JP2021513998A - Enantiomerically enriched or enantiomerically pure bupropion dosage form - Google Patents

Abstract

Described herein are dosage forms of enantiomerically enriched (S) -bupropion or enantiomerically enriched (R) -bupropion. The (S) -bupropion or (R) -bupropion may be deuterium-enriched or may have a natural isotopic abundance. These dosage forms are used to treat the conditions described herein, to achieve specific pharmacokinetic parameters of bupropion or its metabolites, and / or to increase plasma levels of dextromethorphan. It can be administered either by feeding or fasting. [Selection diagram] None

Description

(Cross-reference of related applications)
This application is filed on February 23, 2018, US Provisional Patent Application No. 62 / 634,718, January 18, 2019, 62 / 794,469, and February 22, 2019. Priority is claimed under 62 / 809,480, all of which are incorporated herein by reference in their entirety.

Described herein are dosage forms of enantiomerically enriched (S) -bupropion or enantiomerically enriched (R) -bupropion. The (S) -bupropion or (R) -bupropion may be deuterium-enriched or may have a natural isotope abundance. These dosage forms are used to treat the conditions described herein, to achieve predetermined pharmacokinetic parameters of bupropion or metabolites of bupropion, and / or to increase plasma levels of dextromethorphan. It can be administered either in a feeding or fasting state.

Some embodiments include oral administration of a dosage form containing at least 95% enantiomerically pure about 50 mg to about 100 mg (S) -bupropion to humans at least once daily. Alternatively, it comprises a method of delivering the metabolite to plasma.

Some embodiments select human patients who require bupropion with a pharmacokinetic profile obtained by orally administering a reference dosage form containing a first amount of lasemi-form bupropion at a first dosing frequency. In addition, a dosage form containing at least 95% mirror image isomerically pure second amount of (S) -bupropion is orally administered at the first dose frequency, and the reference dosage form is administered at the first dose frequency. The first dose frequency is once or twice a day, and the second amount is about the first amount, including achieving the same pharmacokinetic profile achieved by administration. Includes a method of delivering bupropion to human plasma, which is 40% to about 60%.

Some embodiments include selecting human patients with symptoms that can be treated by oral administration of a reference dosage form containing a first amount of lasemi-bupropion at a first dosing frequency and at least 95. % Mirror image Achieved by orally administering a second dose of isomerically pure (S) -bupropion-containing dosage form at the first dose frequency and the reference dosage form at the first dose frequency. The first dose frequency is once or twice a day, and the second dose is about 40% to about 60% of the first dose, including achieving the same therapeutic effect as is done. Includes methods of treating conditions that can be treated with lasemi-body bupropion.

Some embodiments treat dextromethorphan and at least 90 mg of at least 95% mirror isomerically pure (S) -bupropion at least once daily with both (S) -bupropion and dextromethorphan. Includes methods of increasing plasma concentrations of (S) -bupropion and dextromethorphan, including oral co-administration to humans in need of (S) -bupropion, wherein the C _max of (S) -bupropion is at least about about in humans. achieved that the 90 ng / mL, the method comprising equal amount of (R) - bupropion and when administered to the human (R) - as compared to the _{C max} of bupropion (S) - the _{C max} of bupropion It has the effect of increasing at least 3 times.

Some embodiments include at least once daily dextromethorphan and at least 90 mg of at least 95% mirror image of isomerically pure (S) -bupropion, (R, R) -hydroxybupropion and dextromethorphan. Includes methods of increasing plasma concentrations of (R, R) -hydroxybupropion and dextromethorphan, including oral co-administration to humans in need of treatment with both, the method of which is (R, R) -hydroxy. Achieving a C _{max of} bupropion of at least about 700 ng / mL in humans, the method achieved that the same amount of (R) -bupropion was administered to the human ((R, R) -hydroxybupropion C _{max). It has the effect of increasing the C max} of (R, R) -hydroxybupropion by at least 3 times.

In some embodiments, at least 90 mg of at least 95% microscopically pure (S) -bupropion is orally administered to humans in need of treatment with (S) -bupropion at least once daily. Includes a method of increasing the plasma concentration of (S) -bupropion, _{which achieves a C min} of (S) -bupropion of at least about 20 ng / mL, the method comprising the same amount of (R). _{) -It has the effect of increasing the C min} of (S) -bupropion by at least 3 times as _{compared with the C min} of (R) -bupropion when the dosage form containing bupropion is administered to the human.

In some embodiments, at least 90 mg of at least 95% microscopically pure (S) -bupropion is orally at least once daily in humans requiring treatment with (R, R) -hydroxybupropion. This method comprises increasing the plasma concentration of (R, R) -hydroxybupropion, including administration, which results in a C _min of (R, R) -hydroxybupropion of at least about 700 ng / mL in humans. _{Has the effect of increasing the C min} of (R, R) -hydroxybupropion by at least 3-fold _{compared to the C min} of (R, R) -hydroxybupropion when the same amount of (R) -bupropion was administered to the human. There is.

Some embodiments include the administration of a therapeutically effective amount of a dosage form containing at least about 95% enantiomerically pure (S) -bupropion and dextromethorphan to the human central nervous system. (CNS) Includes methods of treating disorders.

In some embodiments, a therapeutically effective amount of a dosage form and dextromethorphan containing at least about 95% enantiomerically pure (S) -bupropion is administered to a person in need of treatment with bupropion. Includes a method of increasing the plasma concentration of (S) -bupropion while increasing the plasma concentration of dextromethorphan, including.

Some embodiments comprise a dosage form containing at least about 95% mirror image isomerically pure (R) -bupropion and dextromethorphan, and when the dosage form is orally administered to humans, the same amount of (S) -The plasma concentration of dextromethorphan in humans is enhanced compared to oral administration of a reference dosage form containing bupropion and the same amount of dextromethorphan.

Some embodiments determine the plasma concentration of dextromethorphan in humans, comprising administering to humans a dosage form containing at least about 95% enantiomerically pure (R) -bupropion and dextromethorphan. Including methods of elevation, the dosage form enhances the plasma concentration of dextromethorphan in humans as compared to the reference oral dosage form containing the same amount of (S) -bupropion and the same amount of dextromethorphan.

Some embodiments include administering to a human a dosage form containing at least about 95% enantiomerically pure (S) -bupropion of a therapeutically effective amount to treat the CNS disorder. Includes methods for treating central nervous system (CNS) disorders in humans who are not administered dextromethorphan.

In some embodiments, a therapeutically effective amount of a dosage form containing at least about 95% enantiomerically pure (S) -bupropion and not dextromethorphan is administered to a person in need of treatment with bupropion. Includes methods of increasing plasma concentration of (S) -bupropion, including:

Some embodiments include an oral dosage form containing at least about 90 mg of at least 95% mirror isomer pure (S) -bupropion in humans requiring treatment with (S) -bupropion and dextromethorphan. Includes a method of increasing the plasma concentration of (S) _{-bupropion, including oral administration, which results in a C max} of (S) -bupropion of at least about 90 ng / mL in the human, which method is equivalent. It has the effect of increasing _{the C max} of (S) -bupropion _{by at least 3 times as compared with the C max} of (R) -bupropion when the dosage form containing (R) -bupropion is administered to the human. Humans are not given dextromethorphan.

Some embodiments require treatment of an oral dosage form containing at least about 90 mg of at least 95% mirror isomer pure (S) -bupropion with (R, R) -hydroxybupropion and dextromethorphan. Including a method of increasing the plasma concentration of (R, R) -hydroxybupropion, which comprises oral administration to a human being, the C _max of (R, R) -hydroxybupropion is at least about 90 ng / mL. _{This method compares the C max} of (R, R) -hydroxybupropion when a dosage form containing the same amount of (R) -bupropion is administered to the human, and the C of (R, R) -hydroxybupropion. _{It has the effect of increasing max} by at least 3-fold and the human is not administered dextromethorphan.

Some embodiments include an oral dosage form containing at least 95% enantiomeric excess, and dextromethorphan, the dosage form being the same amount of (S) -bupropion and the same. It increases the plasma concentration of dextromethorphan in humans as compared to the reference oral dosage form containing an amount of dextromethorphan.

Some embodiments include oral dosage forms containing (R) -bupropion and dextromethorphan, the dosage forms day 1 or 8 when administered orally to humans daily for at least 8 consecutive days. The plasma concentration of dextromethorphan in humans of the eye can be enhanced to a much greater extent than the reference oral dosage form, which contains the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion. To do.

Some embodiments include an oral dosage form containing (R) -bupropion and dextromethorphan, wherein the dosage form refers to the reference oral dosage form when administered orally daily to humans for at least 8 consecutive days. _{The average C max} of dextromethorphan in the human on day 1 was increased by at least 150% compared to that on day 1 when the human was orally administered daily for at least 8 consecutive days, and the reference oral dosage form was (S) -Contains the same amount of bupropion and the same amount of dextromethorphan as bupropion.

Some embodiments include an oral dosage form containing (R) -bupropion and dextromethorphan, wherein the dosage form refers to the reference oral dosage form when administered orally daily to humans for at least 8 consecutive days. _{The average C max} of dextromethorphan in the human on day 8 was increased by at least 25% compared to that on day 8 when the human was orally administered daily for at least 8 consecutive days, and the reference oral dosage form was (S) -Contains the same amount of bupropion and the same amount of dextromethorphan as bupropion.

Some embodiments include an oral dosage form containing (R) -bupropion and dextromethorphan, the dosage form being the first day of daily oral administration of the reference dosage form to humans for at least 8 consecutive days. _{The mean C max} of dextromethorphan in the human on day 8 was increased by at least 20-fold, and the reference oral dosage form contained the same amount of bupropion and the same amount of dextromethorphan as lasemi-form bupropion. ..

Some embodiments include an oral dosage form containing (R) -bupropion and dextromethorphan, the dosage form being the first day of daily oral administration of the reference dosage form to humans for at least 8 consecutive days. _{The mean C max} of dextromethorphan in the human on day 1 was increased by at least 60% compared to that, and the reference oral dosage form contained the same amount of bupropion and the same amount of dextromethorphan as lasemi bupropion. ..

Some embodiments include an oral dosage form containing (R) -bupropion and dextromethorphan, wherein the dosage form is day 8 when the reference dosage form is orally administered to humans daily for at least 8 consecutive days. _{The mean C max} of dextromethorphan in the human on day 8 was increased by at least 20%, and the reference oral dosage form contained the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion. ..

Some embodiments include oral administration of the reference dosage form to humans daily for at least 8 consecutive days, comprising oral administration of the dosage form containing (R) -bupropion and dextromethorphan. Including a method of increasing the plasma concentration of dextromethorphan on day 1 or 8 to a much greater extent than the reference dosage form is the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion. Contains.

Some embodiments include methods of treating neuropsychiatric disorders, comprising administering to a person in need of treatment the dosage form described in any of the previous paragraphs.

Some embodiments include methods of treating a cold or cough, comprising administering to a person in need of treatment the dosage form described in any of the previous paragraphs.

Some embodiments include methods of relieving pain, comprising administering to a person in need of treatment the dosage form described in any of the previous paragraphs.

Some embodiments include methods of treating addiction, comprising administering to a person in need of treatment the dosage form described in any of the previous paragraphs.

Some embodiments are humans with symptoms that can be treated with (S) -bupropion once or twice daily in dosage form containing at least 95% mirror image isomer pure (S) -bupropion. The amount of (S) -bupropion administered, including methods of treating humans, including oral administration to, is about 20 of the amount of racemic bupropion administered to treat the same symptoms in the same human. It is selected from% to about 70%.

In some embodiments, at least 95% mirror image of isomerically pure (S) -bupropion is orally administered once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. Including methods that provide therapeutically effective plasma concentrations of (R, R) -hydroxybupropion, (R, R) -hydroxybupropion is present in the human plasma (R, R)-. It is at least 97% of the total amount of hydroxybupropion and (S, S) -hydroxybupropion, which results in a C _max of (R, R) -hydroxybupropion in the human being at least about 500 ng / mL.

Some embodiments include oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion to a person in need of treatment with (S) -bupropion. Including methods of treatment, (S) -bupropion is the only active agent used to treat humans.

Some embodiments are treated with (S) -bupropion once or twice daily in dosage forms containing at least 95% enantiomerically pure (S) -bupropion from about 50 mg to about 100 mg. Includes methods of treating humans, including oral administration to humans in need.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion once or twice daily for humans requiring treatment with (S) -bupropion. Includes methods of treating humans, including oral administration, which results in a C _max of (S) -bupropion of at least about 60 ng / mL.

Some embodiments include dosage forms containing at least 95% mirror image isomerically pure (S) -bupropion in humans requiring treatment with (S) -bupropion once or twice daily. Including methods of treating humans, including oral administration, (R, R) -hydroxybupropions are present in the human plasma (R, R) -hydroxybupropions and (S, S) -hydroxybupropions. At least 97% of the total amount of.

In some embodiments, at least 95% mirror image of isomerically pure (S) -bupropion is orally administered once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. Including methods that provide a therapeutically effective plasma concentration of (R, R) -hydroxybupropion, (R, R) -hydroxybupropion is present in the human plasma (R, R) -hydroxy. At least 97% of the total amount of bupropion and (S, S) -hydroxybupropion.

In some embodiments, at least 95% mirror image of isomerically pure (S) -bupropion is orally administered once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. Including a method of providing a therapeutically effective plasma concentration of (R, R) -hydroxybupropion, which comprises a method that results in a C _max of (R, R) -hydroxybupropion in the human being at least about 500 ng / mL. Become.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion in humans requiring treatment with (S) -bupropion once or twice daily. Includes methods of treating humans, including oral administration, which results in a C _max of (S) -bupropion of at least about 70 ng / mL.

Some embodiments are oral dosage forms containing at least 95% enantiomerically pure (S) -bupropion once or twice daily in humans requiring treatment with (S) -bupropion. Includes methods of treating humans, including administration, which results in an AUC _0-12 of (S) -bupropion at least about 600 ng · h / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion in humans requiring treatment with (S) -bupropion once or twice daily. It comprises a method of treating humans, including oral administration, which results in a C _max of (R, R) -hydroxybupropion of at least about 800 ng / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion once or twice daily for humans requiring treatment with (S) -bupropion. Includes methods of treating humans, including oral administration, which results in an AUC _0-12 of (R, R) -hydroxybupropion at least about 8,000 ng · h / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion in humans requiring treatment with (S) -bupropion once or twice daily. Includes methods of treating humans, including oral administration, which results in a C _max of erythrohydroxybupropion of at least about 90 ng / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion once or twice daily for humans requiring treatment with (S) -bupropion. Includes methods of treating humans, including oral administration, which results in an AUC _0-12 of erythrohydroxybupropion at least about 1,000 ng · h / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion in humans requiring treatment with (S) -bupropion once or twice daily. It comprises a method of treating humans, including oral administration, which results in a C _max of treohydroxybupropion of at least about 450 ng / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion once or twice daily for humans requiring treatment with (S) -bupropion. Includes methods of treating humans, including oral administration, which results in an AUC _0-12 of treohydroxybupropion at least about 5,000 ng · h / mL.

Some embodiments include dosage forms containing at least 95% enantiomerically pure (S) -bupropion.

Some embodiments include administering any of the dosage forms described herein to humans in need of treatment with bupropion or a metabolite thereof (S) -bupropion or a metabolite thereof. Includes methods of increasing plasma concentration.

Some embodiments include methods of treating a neurological condition, comprising administering to a person in need of treatment the dosage form described in any of the previous paragraphs.

Some embodiments include methods of increasing plasma levels of dextromethorphan, comprising administering a combination of (R) -bupropion and dextromethorphan to a person in need of treatment with dextromethorphan. (R) -Bupropion is at least 95% enantiomerically pure.

Some embodiments include orally administering to humans a dosage form containing at least 95% enantiomerically pure (S) -bupropion, a method of delivering (S) -bupropion to human plasma. including.

Some embodiments include oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion to humans, both (R) -bupropion and (S) -bupropion. The C _max of (R) -bupropion is within 20% _{of the C max} of (R) -bupropion when the same amount of racemic bupropion is administered to humans.

Some embodiments include a method of delivering bupropion to human plasma, comprising orally administering to a human a dosage form containing at least 95% mirror image isomerically pure (S) -bupropion. The AUC _0-12 of R) -bupropion is within 20% _{of the AUC 0-12} of (R) -bupropion when the same amount of racemic bupropion is administered to humans.

Some embodiments include a method of delivering bupropion to human plasma, comprising orally administering to human a dosage form containing at least 95% enantiomerically pure (S) -bupropion. The C _max of R, R) -hydroxybupropion is within 20% _{of the C max} of (R, R) -hydroxybupropion when the same amount of racemic bupropion is administered to the human.

Some dosage forms contain enantiomeric excess (S) -bupropion, or enantiomerically pure (S) -bupropion. For example, (S) -bupropion is at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.9%. , Or at least 99.99%, (almost) 100% enantiomer purity. For (S) -bupropion, which has an enantiomer purity of 99.99% (or enantiomeric excess, or 99.99% ee), 99.99% (S) -bupropion and 0.005% [[0]. .01%]] (R) -bupropion is included. For convenience, any of the above may be referred to as "(S) -bupropion". This type of dosage form is a condition in which increasing concentrations of (S) -bupropion and / or (R, R) -hydroxybupropion are therapeutically effective, or in humans (S) -bupropion and / or (R, R). ) -May be useful in the treatment of conditions requiring treatment with hydroxybupropion. Furthermore, for example, an increase in (S) -bupropion concentration or (R, R) -hydroxybupropion concentration due to co-administration of (S) -bupropion and dextromethorphan increases bioavailability or plasma of dextromethorphan. Can be useful for increasing concentrations. Therefore, co-administration of enantiomerically excess (S) -bupropion or enantiomerically pure (S) -bupropion with dextromethorphan in the same or separate dosage forms is dextromethorphan. It may be useful in the treatment of conditions that respond to alone or in combination with (S) -bupropion and dextromethorphan. However, for some treatments, the combination of dextromethorphan with (S) -bupropion or (R, R) -hydroxybupropion may not be desirable. Thus, some dosage forms are substantially free of dextromethorphan, and some treatments include administration of (S) -bupropion without co-administration of dextromethorphan.

In some embodiments, selecting a human patient who requires a pharmacokinetic profile obtained by orally administering a reference dosage form containing a first amount of racemic bupropion at a first dosing frequency, By orally administering a dosage form containing a second amount of (S) -bupropion that is at least 95% mirror image isomerically pure at the first dose frequency and the reference dosage form at the first dose frequency. Including achieving the same pharmacokinetic profile as achieved, the first dose frequency is once or twice daily, and the second amount is about 20-70% of the first amount. , About 40-60%, about 45-55%, or about 50%, a method of providing a pharmacokinetic equivalent of lasemi-bupropion to human plasma. For example, if a particular pharmacokinetic profile is achieved by oral administration of a dosage form containing 150 mg of racemic bupropion and the second amount is 40-60% of the first amount, the second amount is 60-. It is 90 mg. Therefore, in this situation, 60-90 mg (S) -bupropion is administered once daily to achieve a pharmacokinetic profile similar to that achieved by administering 150 mg racemic bupropion once daily. Or 60-90 mg of (S) -bupropion is administered twice daily to achieve a pharmacokinetic profile similar to that achieved by administering 150 mg of racemic bupropion twice daily.

Some embodiments include selecting human patients with symptoms that can be treated by oral administration of a reference dosage form containing a first amount of lasemi-bupropion at a first dosing frequency and at least 95. % Mirror image Achieved by orally administering a second dose of isomerically pure (S) -bupropion-containing dosage form at the first dose frequency and the reference dosage form at the first dose frequency. The first dose frequency is once or twice a day, the second amount is about 40-60% of the first amount, about, including achieving the same therapeutic effect as is done. Includes methods of treating conditions that are treatable by racemic bupropion, which is 45-55%, or about 50%. For example, if a condition can be treated by oral administration of a dosage form containing 150 mg of racemic bupropion and the second amount is 40-60% of the first amount, the second amount is 60-90 mg. Is. Therefore, in this situation, 60-90 mg of (S) -bupropion is administered once daily to obtain a therapeutic effect similar to that achieved by administering 150 mg of racemic bupropion once daily. A condition in which 60-90 mg of (S) -bupropion is administered twice daily to treat the condition or to obtain a therapeutic effect similar to that obtained by administering 150 mg of racemic bupropion twice daily. To treat.

For the purposes of the present disclosure, if the dosage form containing enantiomerically pure (S) -bupropion is found by the FDA to be bioequivalent to the dosage form containing racemic bupropion. The two dosage forms have similar pharmacokinetic profiles.

In some embodiments, (S) - _C max of bupropion, (R) - _C max of bupropion, (S) - bupropion and (R) - _C max combined of bupropion, (R, R) - hydroxy bupropion _C max, (S, S) of - _C max of hydroxy bupropion, (R, R) - hydroxy bupropion and (S, S) - _{C max} combined hydroxy bupropion, _{C max} threo hydroxy bupropion, the erythro hydroxy bupropion C _max , (S) -bupropion AUC _0-12 , (R) -bupropion AUC _0-12 , (S) -bupropion and (R) -bupropion combined AUC _0-12 , (R, R)- hydroxy bupropion _{AUC 0-12, (S, S)} - hydroxy bupropion _{AUC 0-12, (R, R)} - hydroxy bupropion and (S, S) - _{AUC 0-12} combined hydroxy bupropion, threo hydroxy bupropion AUC _0-12 , erythrohydroxybupropion AUC _0-12 , or any combination thereof within 20% of each other. If the value of one dosage form is 1 and the value of the second dosage form is 0.8-1.2, the two dosage forms are considered to be within 20% of each other.

Some dosage forms contain enantiomeric excess (R) -bupropion, or enantiomerically pure (R) -bupropion. For example, (R) -bupropion is at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.9%. , Or at least 99.99%, (almost) 100% enantiomer purity. For convenience, any of the above may be referred to as "(R) -bupropion". This type of dosage form may be useful for increasing bioavailability or increasing plasma levels of dextromethorphan, for example by co-administration of (R) -bupropion with dextromethorphan. Therefore, co-administration of enantiomeric excess (R) -bupropion or enantiomerically pure (R) -bupropion with dextromethorphan in a single or separate dosage form is dextromethorphan. It can be useful in treating conditions that respond to torphans.

The above dosage forms and methods include methods of reducing adverse events associated with treatment with bupropion, methods of increasing plasma concentration of bupropion, such as increasing plasma concentration of (S) -bupropion, and methods of increasing bupropion plasma concentration that need to be administered. It may be incorporated into methods of reducing the dose or frequency of administration without loss of efficacy, improving the therapeutic properties of bupropion, reducing the trough effect of bupropion, or other methods.

The above-mentioned dosage forms and methods for dextromethorphan include methods for increasing the plasma concentration of dextromethorphan, methods for increasing the metabolic time of dextromethorphan, methods for reducing adverse events related to treatment with dextromethorphan, and administration. How to reduce the dose or frequency of administration of dextromethorphan that needs to be done, how to reduce the plasma concentration of dextromethorphan, how to improve the therapeutic properties of dextromethorphan, metabolism of dextromethorphan How to inhibit dextromethorphan, how to correct the high metabolic activity of dextromethorphan, how to improve the antitussive effect of dextromethorphan, how to treat cough, how to reduce the trough effect of dextromethorphan, or other methods It may be incorporated.

In addition, the above dosage forms and methods can be applied to neurological disorders, central nervous system disorders, psychiatric disorders, neuropsychiatric disorders, and related conditions.

Enantiomerically enriched (S) -bupropion, enantiomerically enriched (R) -bupropion, and / or dextromethorphan, as described above or elsewhere in the disclosure. May be administered at least once daily, eg, by oral administration, or for multiple days, such as on multiple consecutive days. For example, enantiomerically enriched (S) -bupropion, alone or in combination with dextromethorphan, once or twice daily, 1, 2, 3, 4, 5, 6, 7, 8, Even if administered for 9 to 13, 14, 15 to 20, 21, 22 to 27, 28, 29, 30, 31, 32 to 59, 60, 61 to 89, 90, or even more consecutive days. Good. Alternatively, the enantiomerically enriched (R) -bupropion, alone or in combination with dextromethorphan, once or twice daily, 1, 2, 3, 4, 5, 6, 7, 8, Even if administered for 9 to 13, 14, 15 to 20, 21, 22 to 27, 28, 29, 30, 31, 32 to 59, 60, 61 to 89, 90, or even more consecutive days. Good. Patients may fast before and / or after oral administration of dosage forms containing (S) -bupropion or (R) -bupropion and / or dextromethorphan.

In some embodiments, the treatment described above involves a dosage form comprising (R) -bupropion or (S) -bupropion, alone or in combination with dextromethorphan, once daily, 1, 2, 3, ,. It may include administration for 4, 5, 6 or 7 days followed by treatment twice daily. For example, a dosage form containing (R) -bupropion or (S) -bupropion is administered once daily on days 1, 2, and 3, and then twice daily from day 4, 2, 3, 4. 5, 6, 7, 8, 9-13, 14, 15-20, 21, 22-27, 28, 29, 30, 31, 32-59, 60, 61-89, 90, or even more Administration was continued for long periods of time, such as consecutive days, or for the rest of the treatment period, twice daily. Starting with once-daily administration for a short period of time and then increasing the dosing frequency twice daily may be useful in reducing the risk of seizures.

(S) -Bupropion has the structure shown below.

Unless otherwise stated, compounds described herein by structure, name, or other means, such as (S) -bupropion, (R) -bupropion, or dextromethorphan, are pharmaceutically acceptable. Other solid forms such as salts, polymorphs, crystals, hydrates, hydrates, etc., deuterium-modified compounds, deuterium-modified compounds such as deuterium-modified dextromethorphan, or the present specification. Includes any chemical species that can be rapidly converted to the compounds described herein under the conditions used as described herein.

For dosage forms containing enantiomeric excess (S) -bupropion, an appropriate amount of (S) -bupropion can be used. In some embodiments, the dosage form is at least about 40 mg, at least about 50 mg, at least about 60 mg, at least about 70 mg, at least about 80 mg, at least about 90 mg, at least about 100 mg, about 4-90 mg, about 50-100 mg, About 50-150 mg, about 70-95 mg, about 50-70 mg, about 60-80 mg, about 60-90 mg, about 70-80 mg, about 70-74 mg, about 72-76 mg, about 74-76 mg, about 74-78 mg, About 70-90 mg, about 90-110 mg, about 90-120 mg, about 100-200 mg, about 100-140 mg, about 140-160 mg, about 160-200 mg, about 104-106 mg, about 100-110 mg, about 110-120 mg, About 120-130 mg, about 130-140 mg, about 140-150 mg, about 145-155 mg, about 148-152 mg, about 150-200 mg, about 200-400 mg, about 250-350 mg, about 280-320 mg, about 290-310 mg, About 200-250 mg, about 250-300 mg, about 70 mg, about 75 mg, about 80 mg, about 100 mg, about 105 mg, about 110 mg, about 150 mg, about 10-50 mg, about 50-100 mg, about 40-90 mg, about 70-95 mg , Or about 50-150 mg of (S) -bupropion, or any amount in the range between these values. In particular, the range obtained includes one or more values for the amount of (S) -bupropion in the dosage form: about 50 mg, about 60 mg, about 75 mg, about 90 mg, about 105 mg, or about 150 mg: Or, if close to, the range of amounts of (S) -Bu obtained by combining either of the above ranges or terminal values is also conceivable. These are values that are potentially considered to have specific utility. Dosage forms containing the above amounts of (S) -bupropion once, twice, or three times daily, i.e. one, two, or three times the above arbitrary dose or dose range per day. The daily dose of 180 to 240 mg, which is twice the amount of 90 to 120 mg, and 270 to 360 mg, which is three times the daily dose of 90 to 120 mg, may be administered. In particular, if the range obtained includes or is close to one or more of the following values: about 150 mg, about 210 mg, or about 250 mg, of any of the above dosage ranges or end values. A daily dose obtained by multiplying the combination and the result by 1, 2, or 3 is also considered. These are values that are potentially considered to have specific utility.

Some of the solid compositions include at least about 5%, at least about 10%, at least about 20%, at least about 50%, at least about 70%, at least about 80%, about 10-30%, about 30 by weight. -50%, about 50-80%, about 80-95%, about 10-50%, about 30-70%, or about 50-90% of (S) -bupropion may be included.

In some embodiments, the dosage form may or may not contain an active agent or drug other than (S) -bupropion. For example, the dosage form may include any active agent of less than 10% by weight, less than 5% by weight, less than 1% by weight, or less than 0.1% by weight by weight of (S) -bupropion. May be included. In some embodiments, the dosage form is less than 10% by weight, less than 5% by weight, less than 1% by weight, or less than 0.1% by weight, based on the weight of (S) -bupropion. It may or may not contain rometorphan or may not contain dextromethorphan. Alternatively, (S) -bupropion may be combined with other compounds such as dextromethorphan in the dosage form.

Administration of (S) -bupropion is at least about 1.1-fold compared to the plasma concentration of (R) -bupropion obtained by administering to the human a dosage form containing the same amount of (R) -bupropion. , At least about 1.2 times, at least about 1.3 times, at least about 1.4 times, at least about 1.5 times, at least about 1.6 times, at least about 1.7 times, at least about 1.8 times, At least about 1.9 times, at least about 2 times, at least about 2.5 times, at least about 3 times, at least about 4 times, at least about 5 times, about 5 to 20 times, at least about 10 times, at least about 20 times, At least about 50 times, at least about 100 times, at least about 150 times, at least about 200 times, or more, about 10 to 15 times, about 10 to 25 times, about 5 to 20 times, about 20 to 30 times, about 30 ~ 40 times, about 40 to 50 times, about 50 to 60 times, about 60 to 70 times, about 70 to 80 times, about 80 to 90 times, about 90 to 100 times, about 100 to 110 times, about 110 to 120 Double, about 120-130 times, about 130-140 times, about 140-150 times, about 150-160 times, about 160-170 times, about 170-180 times, about 180-190 times, or about 190-200 times , (S) -can be useful for increasing plasma concentrations of bupropion.

In some embodiments, the method is standard AUC _{0 compared to AUC 0-12} of (R) -bupropion obtained by administering to humans a dosage form containing the same amount of (R) -bupropion. _{AUC 0-12} of (S) _{-bupropions, such as -12} , mean AUC 0-12, central AUC _0-12 , or individual _{AUC 0-12} , at least about 1.1 times, at least about 1.2. Double, at least about 1.3 times, at least about 1.4 times, at least about 1.5 times, at least about 1.6 times, at least about 1.7 times, at least about 1.8 times, at least about 1.9 times , At least about 2 times, at least about 2.5 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 8 times, at least about 10 times, about 10 times, at least about 15 times, at least about 20 Double, at least about 25 times, at least about 50 times, at least about 100 times, at least about 150 times, at least about 200 times, or more, about 10 to 15 times, about 10 to 25 times, about 5 to 20 times, about 20 to 30 times, about 30 to 40 times, about 40 to 50 times, about 50 to 60 times, about 60 to 70 times, about 70 to 80 times, about 80 to 90 times, about 90 to 100 times, about 100 to 110 times, about 110-120 times, about 120-130 times, about 130-140 times, about 140-150 times, about 150-160 times, about 160-170 times, about 170-180 times, about 180-190 times Or, it has the effect of increasing about 190 to 200 times.

In some embodiments, depending on the method, (S) -bupropion, or (S), such as _{standard AUC 0-12} , average AUC _0-12 , central AUC _0-12 , or individual AUC _{0-12, etc.} ) -Bupropion and (R) -bupropion combined AUC _0-12 has at least about 300 ng · hr / mL, at least about 400 ng · hr / mL, at least about 500 ng · hr / mL, at least about 600 ng · hr / mL, At least about 700 ng · hr / mL, at least about 750 ng · hr / mL, at least about 800 ng · hr / mL, at least about 850 ng · hr / mL, at least about 900 ng · hr / mL, at least about 950 ng · hr / mL, at least about about 1,000 ng · hr / mL, at least about 1,100 ng · hr / mL, at least about 1,200 ng · hr / mL, ~ about 1,200 ng · hr / mL, ~ about 1,300 ng · hr / mL, ~ about 1,400 ng · hr / mL, ~ about 1,500 ng · hr / mL, ~ about 1,600 ng · hr / mL, ~ about 1,700 ng · hr / mL, ~ about 1,800 ng · hr / mL, about 300 ~ 400ng · hr / mL, about 400 ~ 500ng · hr / mL, about 500 ~ 600ng · hr / mL, about 600 ~ 700ng · hr / mL, about 700 ~ 800ng · hr / mL, about 800 ~ 900ng · hr / mL, about 900 to 1,000 ng · hr / mL, about 1,000 to 1,100 ng · hr / mL, about 1,100 to 1,200 ng · hr / mL, about 1,200 to 1,300 ng · hr / mL, about 1,300 to 1,400 ng · hr / mL, about 1,400 to 1,500 ng · hr / mL, about 1,500 to 1,600 ng · hr / mL, about 1,600 to 1,700 ng · hr / mL, about 1,700 to 1,800 ng · hr / mL, about 300 to 600 ng · hr / mL, about 600 to 900 ng · hr / mL, about 900 to 1,200 ng · hr / mL, about 1,200 ~ 1,500 ng · hr / mL, about 1,500 ~ 1,800 ng · hr / mL, about 300 ~ 800 ng · hr / mL, about 800 ~ 1,300 ng · hr / mL, about 1,300 ~ 1,800 ng -Hr / mL, or about 300 to 1,800 ng-hr / mL. In particular, the range obtained is _{the following values for AUC 0-12} : 350 ng · hr / mL, 400 ng · hr / mL, 750 ng · hr / mL, 900 ng · hr / mL, 1,150 ng · hr / mL, or _{AUC 0-12} ranges obtained by combining one or more of the above ranges or terminal values are also conceivable, including or close to one or more values of 1,400 ng · hr / mL. These are values that are potentially considered to have specific utility. The scope of the AUC of interest may be found on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later days.

_{In some embodiments, such as standard C max} , mean C _max , central C _max , or individual C _max, as compared to administration of a dosage form containing the same amount of (R) -bupropion to humans. _{C max} of such (S) -bupropion is at least about 1.1 times, at least about 1.2 times, at least about 1.3 times, at least about 1.4 times, at least about 1.5 times, at least about 1 1.6 times, at least about 1.7 times, at least about 1.8 times, at least about 1.9 times, at least about 2 times, at least about 2.5 times, at least about 3 times, at least about 4 times, at least about 5 times Double, at least about 8 times, about 5 to 20 times, at least about 10 times, about 10 times, at least about 20 times, at least about 25 times, at least about 50 times, at least about 100 times, at least about 150 times, at least about 200 times Double or more, about 10 to 15 times, about 10 to 25 times, about 5 to 20 times, about 20 to 30 times, about 30 to 40 times, about 40 to 50 times, about 50 to 60 times, about 70 ~ 80 times, about 80 to 90 times, about 90 to 100 times, about 100 to 110 times, about 110 to 120 times, about 120 to 130 times, about 130 to 140 times, about 140 to 150 times, about 150 to 160 It has the effect of increasing by a factor of, about 160 to 170 times, about 170 to 180 times, about 180 to 190 times, or about 190 to 200 times.

In some embodiments, depending on the method, (S) -bupropion, or (S) -bupropion and (R)-, such as _{standard C max} , mean C _max , central C _max , or individual C _{max, etc.} The combined C _{max of} bupropion is at least about 30 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, at least about 95 ng / mL, At least about 100 ng / mL, at least about 105 ng / mL, at least about 110 ng / mL, at least about 115 ng / mL, at least about 120 ng / mL, at least about 125 ng / mL, at least about 130 ng / mL, at least about 140 ng / mL, ~ about 130 ng / mL, ~ about 140 ng / mL, ~ about 150 ng / mL, ~ about 160 ng / mL, ~ about 170 ng / mL, ~ about 180 ng / mL, ~ about 190 ng / mL, ~ about 200 ng / mL, ~ about 210 ng / mL, ~ about 220 ng / mL, about 30-40 ng / mL, about 40-50 ng / mL, about 50-60 ng / mL, about 60-70 ng / mL, about 70-80 ng / mL, about 80-90 ng / mL, About 90-100 ng / mL, about 100-110 ng / mL, about 110-120 ng / mL, about 120-130 ng / mL, about 130-140 ng / mL, about 140-150 ng / mL, about 150-160 ng / mL, about 160-170 ng / mL, about 170-180 ng / mL, about 180-190 ng / mL, about 190-200 ng / mL, about 200-210 ng / mL, about 210-220 ng / mL, about 50-70 ng / mL, about 70 ~ 90 ng / mL, about 30-60 ng / mL, about 60-90 ng / mL, about 90-120 ng / mL, about 120-160 ng / mL, about 160-220 ng / mL, about 30-90 ng / mL, about 90- It will be 150 ng / mL, about 150-220 ng / mL, about 30-110 ng / mL, about 130-190 ng / mL, about 110-220 ng / mL, or about 30-220 ng / mL. In particular, if the range obtained _{includes or is close to one or more of the following values for C max} : 45 ng / mL, 90 ng / mL, 130 ng / mL, 160 ng / mL, or 190 ng / mL: Also considered is a _{C max} range obtained by combining either of the above ranges or terminal values. These are values that are potentially considered to have specific utility. The range of C _max of interest may be found on, 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later. ..

_{In some embodiments, standard C min} , mean C _min , central C _min , or individual C _min, etc., as compared to administration of a dosage form containing the same amount of (R) -bupropion to humans. _{C min} of such (S) -bupropion at least about 1.1 times, at least about 1.2 times, at least about 1.3 times, at least about 1.4 times, at least about 1.5 times, at least about 1 1.6 times, at least about 1.7 times, at least about 1.8 times, at least about 1.9 times, at least about 2 times, at least about 2.5 times, at least about 3 times, at least about 4 times, at least about 5 times Double, at least about 8 times, at least about 10 times, at least about 20 times, at least about 50 times, at least about 100 times, at least about 150 times, at least about 200 times, or more, about 10 to 15 times, about 10 to 10 times 25 times, about 5 to 20 times, about 20 to 30 times, about 30 to 40 times, about 40 to 50 times, about 50 to 60 times, about 70 to 80 times, about 80 to 90 times, about 90 to 100 times , About 100 to 110 times, about 110 to 120 times, about 120 to 130 times, about 130 to 140 times, about 140 to 150 times, about 150 to 160 times, about 160 to 170 times, about 170 to 180 times, about It has the effect of increasing 180 to 190 times, or about 190 to 200 times.

In some embodiments, the method, standard _{C min,} mean _{C min,} center _{C min} or such as individual _{C min,,} (S) - _{C min} of bupropion is at least about 20 ng / mL, at least about 25 ng / mL, at least about 30 ng / mL, at least about 35 ng / mL, at least about 40 ng / mL, about 20-60 ng / mL, about 25-30 ng / mL, about 30-35 ng / mL, about 35-40 ng / mL, It will be about 30-40 ng / mL, about 40-45 ng / mL, about 45-50 ng / mL, about 30-50 ng / mL, about 40-50 ng / mL, or about 50-60 ng / mL. In particular, if the range obtained _{includes or is close to one or more of the following values for C min} : 20 ng / mL, 30 ng / mL, 40 ng / mL, or 50 ng / mL: _{A C min} range obtained by combining either the range of or the terminal values is also conceivable. These are values that are potentially considered to have specific utility.

Administration of (S) -bupropion is at least about 1.1 times, at least about 1.5 times, and at least about 2 times that of a human being administered with a dosage form containing the same amount of (R) -bupropion. Double, at least about 3 times, at least about 5 times, at least about 10 times, at least about 15 times, at least about 20 times, at least about 40 times, at least about 50 times, at least about 100 times, at least about 150 times, at least about 200 times Double or more, about 5-10 times, about 5-25 times, about 5-20 times, about 20-30 times, about 30-40 times, about 40-50 times, about 50-60 times, about 70 -80 times, about 80-90 times, about 90-100 times, about 100-110 times, about 110-120 times, about 120-130 times, about 130-140 times, about 140-150 times, about 150-160 It may be useful for increasing plasma concentrations of (R, R) -hydroxybupropion by a factor of, about 160-170, about 170-180, about 180-190, or about 190-200.

Administration of (S) -bupropion is at least about 1.1 times, at least about 1.5 times, and at least about 2 times as compared to the case where the same amount of the dosage form containing (R) -bupropion is administered to humans. Double, at least about 3 times, at least about 5 times, at least about 6 times, at least about 10 times, at least about 15 times, at least about 20 times, at least about 40 times, at least about 50 times, at least about 100 times, at least about 150 Double, at least about 200 times, or more, about 5-10 times, about 5-25 times, about 5-20 times, about 20-30 times, about 30-40 times, about 40-50 times, about 50- 60 times, about 70-80 times, about 80-90 times, about 90-100 times, about 100-110 times, about 110-120 times, about 120-130 times, about 130-140 times, about 140-150 times , About 150-160 times, about 160-170 times, about 170-180 times, about 180-190 times, or about 190-200 times, standard AUC _0-12 , average AUC _0-12 , central AUC _0-12 , _{Alternatively} , it may be useful to increase _{the AUC 0-12} of (R, R) -hydroxybupropions such as individual AUC 0-12.

In some embodiments, the method, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or like individual _{AUC 0-12,, (R, R} ) - hydroxy bupropion, _{Alternatively, AUC 0-12, which} is a combination of (S, S) -hydroxybupropion and (R, R) -hydroxybupropion, is at least about 1,000 ng · hr / mL, at least about 3,000 ng · hr / mL, at least about 4. 000 ng · hr / mL, at least about 6,000 ng · hr / mL, at least about 7,000 ng · hr / mL, at least about 7,500 ng · hr / mL, at least about 8,000 ng · hr / mL, at least about 8 , 500 ng · hr / mL, at least about 9,000 ng · hr / mL, at least about 9,500 ng · hr / mL, at least about 10,000 ng · hr / mL, at least about 12,000 ng · hr / mL, at least about 13 000 ng · hr / mL, about 4,000 to 6,000 ng · hr / mL, about 6,000 to 8,000 ng · hr / mL, about 8,000 to 10,000 ng · hr / mL, about 10,000 ~ 12,000 ng · hr / mL, about 12,000 ~ 14,000 ng · hr / mL, about 14,000 ~ 16,000 ng · hr / mL, about 16,000 ~ 18,000 ng · hr / mL, about 18 000 to 20,000 ng · hr / mL, about 20,000 to 22,000 ng · hr / mL, about 22,000 to 24,000 ng · hr / mL, about 4,000 to 10,000 ng · hr / mL, About 10,000 to 16,000 ng · hr / mL, about 16,000 to 24,000 ng · hr / mL, about 4,000 to 24,000 ng · hr / mL, ~ about 14,000 ng · hr / mL, ~ About 16,000 ng · hr / mL, ~ about 18,000 ng · hr / mL, ~ about 20,000 ng · hr / mL, ~ about 22,000 ng · hr / mL, ~ about 24,000 ng · hr / mL, or It becomes about 30,000 ng · hr / mL. In particular, the range obtained is _{the following values for AUC 0-12} : 4,000 ng · hr / mL, 5,000 ng · hr / mL, 10,000 ng · hr / mL, 13,400 ng · hr / mL, 16. _{AUC 0} obtained by combining one or more values of 000 ng · hr / mL, or 22,000 ng · hr / mL, or close to, either of the above ranges or terminal values. _A range of -12 is also conceivable. These are values that are potentially considered to have specific utility. The scope of the AUC of interest may be found on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later days.

Administration of (S) -bupropion is at least about 1.1 times, at least about 1.2 times, and at least about 1 times as compared to the case where a dosage form containing the same amount of (R) -bupropion is administered to humans. .3 times, at least about 1.4 times, at least about 1.5 times, at least about 1.6 times, at least about 1.7 times, at least about 1.8 times, at least about 1.9 times, at least about 2 times , At least about 2.5 times, at least about 3 times, at least about 4 times, at least about 5 times, about 6 times, at least about 10 times, at least about 20 times, at least about 50 times, at least about 100 times, at least about 150 Double, at least about 200 times, or more, about 5-10 times, about 10-20 times, about 5-20 times, about 20-30 times, about 30-40 times, about 40-50 times, about 50- 60 times, about 70 to 80 times, about 80 to 90 times, about 90 to 100 times, about 100 to 110 times, about 110 to 120 times, about 120 to 130 times, about 130 to 140 times, about 140 to 150 times , About 150-160 times, about 160-170 times, about 170-180 times, about 180-190 times, or about 190-200 times, standard C _max , average C _max , central C _max , or individual C _max, etc. It may be useful to increase _{the C max} of (R, R) -hydroxybupropions such as.

In some embodiments, depending on the method, (R, R) -hydroxybupropion, or (S, S) -hydroxy, such as _{standard C max} , mean C _max , central C _max , or individual C _{max, etc. The combined C max} of bupropion and (R, R) -hydroxybupropion is at least about 90 ng / mL, at least about 150 ng / mL, at least about 200, at least about 300 ng / mL, at least about 400 ng / mL, at least about 500 ng / mL. , At least about 600 ng / mL, at least about 700 ng / mL, at least about 800 ng / mL, at least about 900 ng / mL, at least about 1,000 ng / mL, at least about 1,100 ng / mL, at least about 1,200 ng / mL, at least About 1,300 ng / mL, ~ about 1,400 ng / mL, ~ about 1,500 ng / mL, ~ about 1,600 ng / mL, ~ about 1,700 ng / mL, ~ about 1,800 ng / mL, ~ about 1 , 900 ng / mL, ~ about 2,000 ng / mL, ~ about 2,100 ng / mL, ~ about 2,200 ng / mL, ~ about 2,300 ng / mL, about 300-400 ng / mL, about 400-500 ng / mL , About 500-600 ng / mL, about 600-700 ng / mL, about 700-800 ng / mL, about 800-900 ng / mL, about 900-1,000 ng / mL, about 1,000-1,100 ng / mL, about 1,100 to 1,200 ng / mL, about 1,200 to 1,300 ng / mL, about 1,300 to 1,400 ng / mL, about 1,400 to 1,500 ng / mL, about 1,500 to 1, 600 ng / mL, about 1,600 to 1,700 ng / mL, about 1,700 to 1,800 ng / mL, about 1,800 to 1,900 ng / mL, about 1,900 to 2,000 ng / mL, about 2 000 to 2,100 ng / mL, about 2,100 to 2,200 ng / mL, about 2,200 to 2,300 ng / mL, about 300 to 800 ng / mL, about 800 to 1,300 ng / mL, about 1, It will be 300 to 2,300 ng / mL, or about 300 to 2,300 ng / mL. In particular, the range obtained is one _{of the following values for C max} : 400 ng / mL, 950 ng / mL, 1,100 ng / mL, 1,250 ng / mL, 1,400 ng / mL, or 2,100 ng / mL. If the above values are included or close to the above values, a C _max range obtained by combining either the above range or the terminal values is also conceivable. These are values that are potentially considered to have specific utility. The range of C _max of interest may be found on, 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later. ..

Administration of (S) -bupropion is at least about 1.1 times, at least about 1.2 times, and at least about 1 times as compared to the case where a dosage form containing the same amount of (R) -bupropion is administered to humans. .3 times, at least about 1.4 times, at least about 1.5 times, at least about 1.6 times, at least about 1.7 times, at least about 1.8 times, at least about 1.9 times, at least about 2 times , At least about 2.5 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 10 times, at least about 20 times, at least about 50 times, at least about 60 times, at least about 100 times, at least about 150 times, at least about 200 times, or more, about 1 to 5 times, about 5 to 10 times, about 5 to 20 times, about 20 to 30 times, about 30 to 40 times, about 40 to 50 times, about 50 times ~ 60 times, about 60 to 70 times, about 70 to 80 times, about 80 to 90 times, about 90 to 100 times, about 100 to 110 times, about 110 to 120 times, about 120 to 130 times, about 130 to 140 Double, about 140-150 times, about 150-160 times, about 160-170 times, about 170-180 times, about 180-190 times, or about 190-200 times, standard C _min , average C _min , central C _min , Or can be useful for increasing _{the C min} of (R, R) -hydroxybupropions, such as _{individual C min.}

In some embodiments, the method, standard _{C min,} mean _{C min,} center _{C min} or such as individual _{C min,,} (R, R) - _{C min} of hydroxy bupropion is at least about 150 ng / mL , At least about 200 ng / mL, at least about 300 ng / mL, at least about 400 ng / mL, at least about 500 ng / mL, at least about 600 ng / mL, at least about 700 ng / mL, at least about 800 ng / mL, at least about 900 ng / mL, at least About 1,000 ng / mL, at least about 1,100 ng / mL, at least about 1,200 ng / mL, ~ about 1,300 ng / mL, ~ about 1,400 ng / mL, ~ about 1,500 ng / mL, ~ about 1 , 600 ng / mL, ~ about 1,700 ng / mL, ~ about 1,800 ng / mL, ~ about 1,900 ng / mL, ~ about 2,000 ng / mL, ~ about 2,100 ng / mL, ~ about 2,200 ng / ML, ~ about 2,300 ng / mL, about 200-300 ng / mL, about 300-400 ng / mL, about 400-500 ng / mL, about 500-600 ng / mL, about 600-700 ng / mL, about 700-800 ng / ML, about 800 to 900 ng / mL, about 900 to 1,000 ng / mL, about 1,000 to 1,100 ng / mL, about 1,100 to 1,200 ng / mL, about 1,200 to 1,300 ng / mL mL, about 1,300-1,400 ng / mL, about 1,400-1,500 ng / mL, about 1,500-1,600 ng / mL, about 300-700 ng / mL, about 700-1,100 ng / mL , About 1,100 to 1,600 ng / mL, or about 800 to 1,200 ng / mL. In particular, the range obtained is _{one or more of the following values for C min} : 350 ng / mL, 600 ng / mL, 800 ng / mL, 1,000 ng / mL, 1,200 ng / mL, or 1,400 ng / mL. _{A C min} range obtained by combining either the above range or the terminal values is also conceivable if it includes or is close to the values. These are values that are potentially considered to have specific utility.

Administration of (S) -bupropion to humans results in (R, R) -hydroxybupropion being present in the human plasma of (R, R) -hydroxybupropion and (S, S) -hydroxybupropion. Can be at least 90%, at least 95%, at least 97%, at least 97.2%, at least 97.4%, at least 97.6%, at least 97.8%, or at least 98% of the total amount of.

In some embodiments, the method, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or like individual _{AUC 0-12,} erythro _{AUC 0-12} of hydroxy bupropion, is At least about 500 ng · hr / mL, at least about 600 ng · hr / mL, at least about 800 ng · hr / mL, at least about 1,000 ng · hr / mL, at least about 1,200 ng · hr / mL, at least about 1,400 ng ·. hr / mL, at least about 1,500 ng · hr / mL, at least about 1,600 ng · hr / mL, at least about 1,800 ng · hr / mL, at least about 2,000 ng · hr / mL, ~ about 1,400 ng · hr / mL, ~ about 1,600 ng · hr / mL, ~ about 1,800 ng · hr / mL, ~ about 2,000 ng · hr / mL, ~ about 2,200 ng · hr / mL, ~ about 2,400 ng · hr / mL, ~ about 2,600 ng · hr / mL, ~ about 2,800 ng · hr / mL, ~ about 3,000 ng · hr / mL, about 500 ~ 600 ng · hr / mL, about 600 ~ 800 ng · hr / mL, about 800 to 1,000 ng · hr / mL, about 1,000 to 1,200 ng · hr / mL, about 1,200 to 1,400 ng · hr / mL, about 1,400 to 1,600 ng · hr / mL, about 1,600 to 1,800 ng · hr / mL, about 1,800 to 2,000 ng · hr / mL, about 2,000 to 2,200 ng · hr / mL, about 2,200 to 2,400 ng · hr / mL, about 2,400 to 2,600 ng · hr / mL, about 2,600 to 2,800 ng · hr / mL, about 2,800 to 3,000 ng · hr / mL, about 500 to 1,000 ng · hr / mL, about 1,000 to 1,500 ng · hr / mL, about 1,500 to 2,000 ng · hr / mL, about 2,000 to 2,500 ng · hr / mL, about 2,500 to 3, 000 ng · hr / mL, about 500 to 1,500 ng · hr / mL, about 1,500 to 3,000 ng · hr / mL, about 2,000 to 3,000 ng · hr / mL, or about 500 to 3,000 ng・ It becomes hr / mL. In particular, the range obtained is _{the following values for AUC 0-12} : 500 ng · hr / mL, 1,300 ng · hr / mL, 1,500 ng · hr / mL, 1,800 ng · hr / mL, or. _{AUC 0-12} ranges obtained by combining any of the above ranges or terminal values are also conceivable, including or close to one or more values of 2,600 ng · hr / mL. These are values that are potentially considered to have specific utility. The scope of the AUC of interest may be found on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later days.

In some embodiments, the method, standard _{C max,} mean _{C max, C max} of such erythro hydroxy bupropion like central _{C max} or individual _{C max,} is at least about 40 ng / mL, at least about 60 ng / mL , At least about 80 ng / mL, at least about 90 ng / mL, at least about 100 ng / mL, at least about 120 ng / mL, at least about 140 ng / mL, at least about 160 ng / mL, at least about 180 ng / mL, at least about 200 ng / mL, About 160 ng / mL, ~ about 180 ng / mL, ~ about 200 ng / mL, ~ about 220 ng / mL, ~ about 240 ng / mL, ~ about 260 ng / mL, ~ about 280 ng / mL, about 40-60 ng / mL, about 60 ~80ng / mL, about 80~100ng / mL, about _{10 0~12 0ng} / mL, about 120~140ng / mL, about 140~160ng / mL, about 160~180ng / mL, about 180~200ng / mL, about 200-220 ng / mL, about 220-240 ng / mL, about 240-260 ng / mL, about 260-280 ng / mL, about 280-300 ng / mL, about 40-100 ng / mL, about 100-150 ng / mL, about 150 ~ 200 ng / mL, about 200-250 ng / mL, about 250-280 ng / mL, about 40-120 ng / mL, about 120-200 ng / mL, about 200-280 ng / mL, or about 40-280 ng / mL. In particular, if the range obtained _{includes or is close to one or more of the following values for C max} : 60 ng / mL, 120 ng / mL, 130 ng / mL, 200 ng / mL, or 240 ng / mL: Also considered is a _{C max} range obtained by combining either of the above ranges or terminal values. These are values that are potentially considered to have specific utility. The range of C _max of interest may be found on, 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later. ..

In some embodiments, the method, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or like individual _{AUC 0-12,, AUC 0-12} threo hydroxy bupropion, At least 1,000 ng · hr / mL, at least about 2,000 ng · hr / mL, at least about 3,000 ng · hr / mL, at least about 4,000 ng · hr / mL, at least about 5,000 ng · hr / mL, at least About 6,000 ng · hr / mL, at least about 7,000 ng · hr / mL, at least about 8,000 ng · hr / mL, ~ about 8,000 ng · hr / mL, ~ about 9,000 ng · hr / mL, ~ About 10,000 ng · hr / mL, ~ about 11,000 ng · hr / mL, ~ about 12,000 ng · hr / mL, ~ about 13,000 ng · hr / mL, ~ about 14,000 ng · hr / mL, ~ About 15,000 ng · hr / mL, about 2,000 to 15,000 ng · hr / mL, about 2,000 to 3,000 ng · hr / mL, about 3,000 to 4,000 ng · hr / mL, about 4 5,000 to 5,000 ng · hr / mL, about 5,000 to 6,000 ng · hr / mL, about 6,000 to 7,000 ng · hr / mL, about 7,000 to 8,000 ng · hr / mL, About 8,000 to 9,000 ng · hr / mL, about 9,000 to 10,000 ng · hr / mL, about 10,000 to 11,000 ng · hr / mL, about 11,000 to 12,000 ng · hr / mL, about 12,000 to 13,000 ng · hr / mL, about 13,000 to 14,000 ng · hr / mL, about 14,000 to 15,000 ng · hr / mL, about 2,000 to 6,000 ng · hr / mL, about 6,000 to 10,000 ng · hr / mL, about 10,000 to 15,000 ng · hr / mL, about 2,000 to 9,000 ng · hr / mL, or about 9,000 to 15 It becomes 000 ng · hr / mL. In particular, the range obtained is _{the following values for AUC 0-12} : 3,000 ng · hr / mL, 6,000 ng · hr / mL, 8,000 ng · hr / mL, or. _{AUC 0-12} ranges obtained by combining one or more of the above ranges or terminal values are also conceivable, including or close to one or more values of 12,000 ng · hr / mL. These are values that are potentially considered to have specific utility. The scope of the AUC of interest may be found on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later days.

In some embodiments, the method, standard _{C max,} mean _{C max, C max} of a threo hydroxy bupropion like central _{C max} or individual _{C max,} is at least about 200 ng / mL, at least about 300 ng / mL , At least about 400 ng / mL, at least about 450 ng / mL, at least about 500 ng / mL, at least about 600 ng / mL, at least about 700 ng / mL, at least about 800 ng / mL, ~ about 800 ng / mL, ~ about 900 ng / mL, ~ About 1,000 ng / mL, ~ about 1,100 ng / mL, ~ about 1,200 ng / mL, ~ about 1,300 ng / mL, ~ about 1,400 ng / mL, about 200 to 300 ng / mL, about 300 to 400 ng / ML, about 400-500 ng / mL, about 500-600 ng / mL, about 600-700 ng / mL, about 700-800 ng / mL, about 800-900 ng / mL, about 900-1000 ng / mL, about 1,000- 1,100 ng / mL, about 1,100 to 1,200 ng / mL, about 1,200 to 1,300 ng / mL, about 1,300 to 1,400 ng / mL, about 200 to 500 ng / mL, about 500 to 800 ng / ML, about 800-1,100 ng / mL, about 1,100-1,400 ng / mL, about 200-800 ng / mL, about 800-1400 ng / mL, 400-600 ng / mL, or about 200-1,400 ng It becomes / mL. In particular, the range obtained _{will include or include one or more of the following values for C max} : 300 ng / mL, 500 ng / mL, 600 ng / mL, 900 ng / mL, or 1,200 ng / mL: _{If close, a C max} range obtained by combining either of the above ranges or the terminal values is also conceivable. These are values that are potentially considered to have specific utility. The range of C _max of interest may be found on, 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, or later. ..

(R) -Bupropion has the structure shown below.

For dosage forms containing enantiomeric excess (R) -bupropion, an appropriate amount of (R) -bupropion can be used. In some embodiments, the dosage form is at least about 80 mg, at least about 90 mg, at least about 100 mg, about 90-110 mg, about 100-200 mg, about 100-150 mg, about 100-140 mg, about 140-160 mg, about. 160-200 mg, about 104-106 mg, about 100-110 mg, about 110-120 mg, about 120-130 mg, about 130-140 mg, about 140-150 mg, about 145-155 mg, about 148-152 mg, about 150-200 mg, about 200-400 mg, about 250-350 mg, about 280-320 mg, about 290-310 mg, about 200-250 mg, about 250-300 mg, about 100 mg, about 105 mg, about 110 mg, or about 150 mg of (R) -bupropion, or these. Includes any amount in the range between the values of. Such a dosage form may be administered with dextromethorphan, and dextromethorphan may be administered in a different or the same dosage form as (R) -bupropion. Dosage forms containing the above amounts of (R) -bupropion at one, two, or three times the daily dose of any of the above doses or dose ranges, once, twice, or 3 times daily. It may be administered in multiple doses.

In some embodiments, the dosage form may or may not contain an active agent or drug other than (R) -bupropion and / or dextromethorphan. For example, the dosage form is less than 10% by weight, less than 5% by weight, less than 1% by weight, or less than 0.1% by weight, based on the combined weight of (R) bupropion and dextromethorphan. Any active agent may be included.

Some of the solid compositions include at least about 5% (w / w), at least about 10% (w / w), at least about 20% (w / w), at least about 50% (w / w), At least about 70% (w / w), at least about 80%, about 10% (w / w) to about 30% (w / w), about 10% (w / w) to about 20% (w / w) , About 20% (w / w) to about 30% (w / w), about 30% (w / w) to about 50% (w / w), about 30% (w / w) to about 40% ( w / w), about 40% (w / w) to about 50% (w / w), about 50% (w / w) to about 80% (w / w), about 50% (w / w) About 60% (w / w), about 60% (w / w) to about 70% (w / w), about 70% (w / w) to about 80% (w / w), or about 80% ( W / w) to about 90% (w / w) of (R) -bupropion may be included.

As explained above, dosage forms containing enantiomeric excess (S) -bupropion or enantiomeric excess (R) -bupropion may be administered with dextromethorphan, depending on the particular need for treatment. May also contain dextromethorphan.

Dextromethorphan has the structure shown below.

Unless otherwise stated, compounds described herein by structure, name, or other means, such as (S) -bupropion, (R) -bupropion, and / or dextromethorphan, may be included. Other solid forms such as pharmaceutically acceptable salts, polymorphs, crystals, solvates, hydrates, etc., deuterates, deuterium-modified compounds such as deuterium-modified dextromethorphan, or Includes any chemical species that can be rapidly converted to the compounds described herein under the conditions used as described herein.

Dextromethorphan may be deuterium-enriched or may have a natural isotope abundance.

Dextromethorphan is used as a cough suppressant. According to the FDA's labeling requirements for dextromethorphan products based on the OTC monograph [21CFR341.74], dextromethorphan is 6 times a day (every 4 hours), 4 times a day (every 6 hours), or 1 day. It should be administered 3 times (every 8 hours).

Dextromethorphan is rapidly metabolized in the human liver. This rapid hepatic metabolism can limit systemic drug exposure in individuals with high metabolic activity. Humans are 1) a group with high dextromethorphan metabolic activity-humans who rapidly metabolize dextromethorphan, 2) a group with low dextromethorphan metabolic activity-humans who cannot sufficiently metabolize dextromethorphan, and 3) dextromethorphan. The group in which the metabolic activity of torphan is intermediate-the human whose metabolism of dextromethorphan is somewhere between the group with high metabolic activity and the group with low metabolic activity can be. The group with high metabolic activity can also be an ultra-rapid metabolic group. The group with high metabolic activity of dextromethorphan accounts for the majority of the human population. Dextromethorphan (DM) can be metabolized to, for example, dextromethorphan (DX). The DM / DX ratio is often used to describe the degree of metabolism of dextromethorphan. The lower the DM / DX ratio, the higher the degree of metabolism of dextromethorphan. People with a DM / DX ratio of less than 0.3 are usually considered to be a highly metabolically active phenotype.

When the same dose of oral dextromethorphan is administered, the plasma concentration of dextromethorphan is low or intermediate in metabolic activity compared to the high metabolic activity group of dextromethorphan. Remarkably high in the group. Low plasma concentrations of dextromethorphan can limit its clinical usefulness as a single agent for groups with high metabolic activity and possibly intermediate metabolic activity. Some therapeutically active compounds, including antidepressants such as (S) -bupropion or (R) -bupropion, inhibit the metabolism of dextromethorphan and increase plasma levels of dextromethorphan, thus treating it. The effect can be improved. Similarly, with (S) -bupropion or (R) -bupropion, once a day instead of twice a day, once a day instead of three times a day, once a day instead of four times a day The frequency of administration of dextromethorphan can be reduced without impairing the therapeutic effect, such as twice a day instead of three times a day and twice a day instead of four times a day. (S) -bupropion and / or (R) -bupropion can also reduce a single dose and / or total amount of dextromethorphan.

Dosage forms containing dextromethorphan used for this purpose are either administered as an adjunct dosage form or combined with (S) -bupropion or (R) -bupropion in a single dosage form. About 1 to 150 mg, about 10 to 100 mg, about 10 to 50 mg, about 20 to 50 mg, about 10 to 20, about 15 to 25, about 20 to 30, about 25 to 35, about 30 to 40, about 35. ~ 45, about 30-50 mg, about 40-50 mg, about 43-48 mg, about 44-46 mg, about 50-100 mg, about 50-80 mg, about 80-100 mg, about 85-95 mg, about 88-92 mg, about 100 Appropriate amounts of dextromethorphan, such as ~ 150 mg, about 30 mg, about 45 mg, or about 60 mg dextromethorphan, or any amount of dextromethorphan in the range between these values, may be included. Dosage forms containing the above amounts of dextromethorphan are administered once, twice, or three times daily at a daily dose of one, two, or three times the above arbitrary dose or dose range. You may.

Some of the solid compositions include at least about 5% (w / w), at least about 10% (w / w), at least about 20% (w / w), at least about 50% (w / w), At least about 70% (w / w), at least about 80%, about 10% (w / w) to about 30% (w / w), about 10% (w / w) to about 20% (w / w) , About 20% (w / w) to about 30% (w / w), about 30% (w / w) to about 50% (w / w), about 30% (w / w) to about 40% ( w / w), about 40% (w / w) to about 50% (w / w), about 50% (w / w) to about 80% (w / w), about 50% (w / w) About 60% (w / w), about 60% (w / w) to about 70% (w / w), about 70% (w / w) to about 80% (w / w), or about 80% ( W / w) to about 90% (w / w) of dextromethorphan may be included.

(S) -bupropion, (R) -bupropion, and / or dextromethorphan are used in selected routes of administration and standard pharmaceutical practices, as described, for example, in Remington's Pharmaceutical Sciences, 2005. It may be combined with a pharmaceutical carrier selected based on it. The relative ratio of active ingredient to carrier can be determined, for example, by the solubility and chemistry of the compound, the route of administration chosen, and standard pharmaceutical practices.

(S) -bupropion, (R) -bupropion, and / or dextromethorphan may be administered to human patients in various forms, eg, orally or parenterally, for the route of administration chosen. Parenteral administration in this regard includes the following routes: intravenous, intramuscular, subcutaneous, intraocular, intrasulous, transepithelial including transdermal, eye drops, sublingual, oral, local including eye, dermis, Includes ocular, transrectal, and nasal administration.

(S) -bupropion, (R) -bupropion, and / or dextromethorphan may be formulated for oral administration, eg, with an inert diluent or with an edible carrier, hard or softshell gelatin capsules. , May be encapsulated in tablets, or may be incorporated directly into the diet. For oral therapeutic administration, the active compound can be incorporated into excipients and used in the form of ingestible tablets, oral tablets, troches, capsules, elixirs, suspensions, syrups, wafers and the like.

Tablets, troches, pills, capsules, etc. containing (S) -bupropion, (R) -bupropion, and / or dextrometorfan include: tragant gum, acacia, cornstarch, binders such as gelatin, dicalcium phosphate, etc. Excipients, cornstarch, pastille starch, disintegrants such as alginic acid, lubricants such as magnesium stearate, sweeteners such as sucrose, lactose and saccharin, or fragrances such as peppermint, winter green oil and sacranbo. It may contain 1 or more. When the dosage form is a capsule, it may contain a liquid carrier in addition to the above materials. Various other materials may be present as coatings, for example tablets, pills, or capsules may be coated with shellac, sugar, or both. The syrup or elixir may contain active compounds, sucrose as a sweetener, methyl and propylparabens as preservatives, dyes, and flavors such as cherry or orange flavors. It is desirable that the material in the dosage form or pharmaceutical composition be pharmaceutically pure and substantially non-toxic in the amount used.

Some compositions or dosage forms may be liquid or may contain a solid phase dispersed in the liquid.

(S) -bupropion, (R) -bupropion, and / or dextromethorphan may be formulated for parenteral or intraperitoneal administration. A solution of the active compound as a free base or a pharmaceutically acceptable salt can be prepared by appropriately mixing with a detergent in water. The dispersion can also have oil dispersed in glycerol, liquid polyethylene glycol, and mixtures thereof. Under normal conditions of storage and use, these preparations may contain preservatives to prevent the growth of microorganisms.

The dosage form or composition containing both (S) -bupropion or (R) -bupropion and dextromethorphan may be a blend or mixture of bupropion and dextromethorphan, alone or in a solvent. .. For example, (S) -bupropion or (R) -bupropion and dextromethorphan may be dispersed with each other or both dispersed in a solvent. The dispersion may contain a mixture of solid materials in which the individual particles are substantially one compound, where the individual particles are a blend of two powders of two different agents with a solid solvent. They are dispersed together and the blending is done in a solid state, as can happen in some cases. In some embodiments, dextromethorphan and (S) -bupropion or (R) -bupropion may be substantially non-uniformly dispersed within the composition or dosage form. Alternatively, dextromethorphan and (S) -bupropion or (R) -bupropion may be present in separate regions or phases within the composition or dosage form. For example, one drug may be in the coating and another may be in the core in the coating. For example, one drug may be formulated as sustained release and another drug may be formulated as immediate release.

Some embodiments include administration of tablets containing a sustained release form of (S) -bupropion or (R) -bupropion and, if present, an immediate release form of dextromethorphan. There are many ways in which sustained release of bupropion can be achieved, but in some embodiments, (S) -bupropion or (R) -bupropion is combined with hydroxypropyl methylcellulose. For example, particles of (S) -bupropion or (R) -bupropion can be mixed with microcrystalline cellulose and hydroxypropyl methylcellulose (eg, METHOCEL®) to form a blended powder mixture. It can then be combined with immediate-release dextromethorphan in a single tablet.

By administering the combination of (R) -bupropion and dextromethorphan to humans in need of treatment with dextromethorphan, it is compared with the administration of the same amount of (S) -bupropion and the same amount of dextromethorphan. Then, the concentration of dextromethorphan can be increased. In some embodiments, administration of the same amount of (S) -bupropion plus the same amount of dextromethorphan is administered, such as standard C _max , mean C _max , central C _max , or individual C _max . _{C max} of dextromethorphan as standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or dextromethorphan _{AUC 0-12} such as individual _{AUC 0-12,} standard AUC _{0 Dextromethorphan AUC 0-∞,} such as _−∞ , mean AUC _0-∞ , central AUC _0-∞ , or individual _{AUC 0-∞} , at least about 10%, at least about 20%, at least about 25%. , At least about 30%, at least about 35%, at least about 40%, at least about 50%, at least about 80%, at least about 100%, at least about 150%, or at least about 200%. This increase is seen on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, or 8th days of treatment, or later. In some embodiments, this increase is seen on day one. In some embodiments, this increase is seen on day 8.

In some embodiments, the combination of (R) -bupropion and dextrometholphan, such as standard AUC _0-12 , average AUC _0-12 , central AUC _0-12 , or individual AUC _0-12, etc. Rometorphan AUC _0-12 is, for example, on days 1-60, about 30-150 ng · hr / mL, about 50-100 ng · hr / mL, about 80-100 ng · hr / mL, about 400-425 ng · hr. / ML, about 425-450 ng · hr / mL, about 400-450 ng · hr / mL, about 450-475 ng · hr / mL, about 475-500 ng · hr / mL, about 450-500 ng · hr / mL, about 500 ~ 510 ng · hr / mL, about 510-520 ng · hr / mL, about 520-530 ng · hr / mL, about 530-540 ng · hr / mL, about 540-560 ng · hr / mL, about 500 ~ 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 ~ 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / mL , About 850-860 ng · hr / mL, about 860-870 ng · hr / mL, about 870-880 ng · hr / mL, about 880-890 ng · hr / mL, about 890-900 ng · hr / mL, about 850-900 ng -Hr / mL, about 900-910 ng-hr / mL, about 910-930 ng-hr / mL, about 930-950 ng-hr / mL, about 900-950 ng-hr / mL, about 950-1000 ng-hr / mL, It can be _{AUC 0-12} for any dextrometrifan in the range of about 1000 ng · hr / mL to about 1300 ng · hr / mL, or between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} day 5, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} on day 6 days, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} on day 7, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} the eighth day, approximately 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, about 1000 ng · hr / mL to about 1300 ng · hr / mL, or any dextrometrifan in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} in 9 days, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} the 10th day, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} the 11th day, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, (R) - The combination of bupropion and dextromethorphan, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} of dextromethorphan such as individual _{C max,} is, for example On days 1-60, at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least About 80 ng / mL, at least about 90 ng / mL, about 2-20 ng / mL, 5-10 ng / mL, about 10-15 ng / mL, about 40-43 ng / mL, about 43-45 ng / mL, about 40-45 ng / mL mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL , About 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65-70 ng / mL, About 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng / mL, about 93 It can be ~ 95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, about 100-110 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} of dextromethorphan such as individual _{C max} on day 5, at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} is 6 days of dextromethorphan such as individual _{C max,,} at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} is day 7 of dextromethorphan such as individual _{C max,,} at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} is day 8 of dextromethorphan such as individual _{C max,,} at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, about 100-110 ng / mL, or any C _{max in the range between these values.} ..

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} is day 09 of dextromethorphan such as individual _{C max,,} at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or individual _{C max C max} of dextromethorphan, such as day 10, at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (R) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (R) -bupropion twice daily. administration, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} of dextromethorphan such as individual _{C max} on day 11, at least about 10 ng / mL, at least about 20 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, at least about 60 ng / mL, at least about 70 ng / mL, at least about 80 ng / mL, at least about 90 ng / mL, about 40-43 ng / mL, about 43- 45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / ML, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL mL, about 65-70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL , About 85-86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, It can be about 91-93 ng / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

The dextromethorphan coefficient of variation FI (%) can be calculated by the following equation.

In some embodiments, a combination of (R) -bupropion and dextromethorphan, eg, administration of about 30-60 mg of dextromethorphan daily, and administration of about 50-150 mg of (R) -bupropion twice daily. Dextromethorphan FI (%), such as standard FI (%), average FI (%), central FI (%), or individual FI (%), is less than 100%, 50 on day 8. It can be less than%, less than 40%, less than 30%, about 20-50%, about 20-40%, about 20-30%, or any FI (%) in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextromethorphan, eg, administration of about 30-60 mg of dextromethorphan daily, and administration of about 50-150 mg of (R) -bupropion twice daily. Dextromethorphan FI (%), such as standard FI (%), average FI (%), central FI (%), or individual FI (%), is less than 100%, 50 on day 9. It can be less than%, less than 40%, less than 30%, about 20-50%, about 20-40%, about 20-30%, or any FI (%) in the range between these values.

In some embodiments, a combination of (R) -bupropion and dextromethorphan, eg, administration of about 30-60 mg of dextromethorphan daily, and administration of about 50-150 mg of (R) -bupropion twice daily. Dextromethorphan FI (%), such as standard FI (%), average FI (%), central FI (%), or individual FI (%), is less than 100%, 50 on day 10. It can be less than%, less than 40%, less than 30%, about 20-50%, about 20-40%, about 20-30%, or any FI (%) in the range between these values.

By administering the combination of (R) -bupropion and dextromethorphan to humans in need of treatment with dextromethorphan, it is compared with the administration of the same amount of (S) -bupropion and the same amount of dextromethorphan. Thus, the concentration of dextromethorphan can be increased, but administration of the combination of (S) -bupropion and dextromethorphan is compared to administration of dextromethorphan without administration of (S) -bupropion. , The plasma concentration of dextromethorphan can be increased.

In some embodiments, the combination of R) -bupropion and dextromethorphan is administered to a person in need of treatment with dextromethorphan to give the same amount of racemic bupropion and dextromethorphan. In comparison, the concentration of dextromethorphan can be increased. In some embodiments, such an increase can be significant or significant.

In some embodiments, depending on the combination of (S) -bupropion and dextrometr _fan , a dext such as _{standard AUC 0-12} , average AUC _0-12 , central AUC 0-12, or individual AUC _{0-12, etc.} Rometorphan AUC _0-12 is, for example, on days 1-60, about 10-50 ng · hr / mL, about 20-40 ng · hr / mL, about 30-100 ng · hr / mL, about 400-425 ng · hr. / ML, about 425-450 ng · hr / mL, about 400-450 ng · hr / mL, about 450-475 ng · hr / mL, about 475-500 ng · hr / mL, about 450-500 ng · hr / mL, about 500 ~ 510 ng · hr / mL, about 510-520 ng · hr / mL, about 520-530 ng · hr / mL, about 530-540 ng · hr / mL, about 540-560 ng · hr / mL, about 500 ~ 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 ~ 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / mL , About 850-860 ng · hr / mL, about 860-870 ng · hr / mL, about 870-880 ng · hr / mL, about 880-890 ng · hr / mL, about 890-900 ng · hr / mL, about 850-900 ng -Hr / mL, about 900-910 ng-hr / mL, about 910-930 ng-hr / mL, about 930-950 ng-hr / mL, about 900-950 ng-hr / mL, about 950-1000 ng-hr / mL, It can be about 1000-1100 ng · hr / mL, or AUC _0-12 for any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} day 5, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} on day 6 days, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} on day 7, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} the eighth day, approximately 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, about 1000-1100 ng · hr / mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} in 9 days, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} the 10th day, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. administration, standard _{AUC 0-12,} mean _{AUC 0-12,} center _{AUC 0-12} or _{AUC 0-12} of dextromethorphan, such as individual _{AUC 0-12,} the 11th day, about 400~425ng -Hr / mL, about 425-450 ng-hr / mL, about 400-450 ng-hr / mL, about 450-475 ng-hr / mL, about 475-500 ng-hr / mL, about 450-500 ng-hr / mL, About 500 to 510 ng · hr / mL, about 510 to 520 ng · hr / mL, about 520 to 530 ng · hr / mL, about 530 to 540 ng · hr / mL, about 540 to 560 ng · hr / mL, about 500 to 550 ng · hr / mL, about 550-575 ng · hr / mL, about 575-600 ng · hr / mL, about 550-600 ng · hr / mL, about 600-650 ng · hr / mL, about 650-700 ng · hr / mL, about 700 to 750 ng · hr / mL, about 750 to 800 ng · hr / mL, about 800 to 820 ng · hr / mL, about 820 to 840 ng · hr / mL, about 840 to 850 ng · hr / mL, about 800 to 850 ng · hr / ML, about 850 to 860 ng · hr / mL, about 860 to 870 ng · hr / mL, about 870 to 880 ng · hr / mL, about 880 to 890 ng · hr / mL, about 890 to 900 ng · hr / mL, about 850 ~ 900 ng · hr / mL, about 900 ~ 910 ng · hr / mL, about 910-930 ng · hr / mL, about 930-950 ng · hr / mL, about 900 ~ 950 ng · hr / mL, about 950-1000 ng · hr / It can be _{AUC 0-12 in} mL, or any dextrometholphan in the range between these values.

In some embodiments, (S) - The combination of bupropion and dextromethorphan, standard _{C max,} mean _{C max,} the central _{C max} or _{C max} of dextromethorphan such as individual _{C max,} is, for example On days 1-60, about 1-10 ng / mL, about 2-5 ng / mL, about 5-10 ng / mL, about 40-43 ng / mL, about 43-45 ng / mL, about 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54 ~ 56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65-70 ng / mL, about 70- 75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85-86 ng / mL, about 86-87 ng / ML, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng / mL, about 93-95 ng / mL It can be mL, about 90-95 ng / mL, about 95-100 ng / mL, about 100-110 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 5. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 6. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 7. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 8. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, about 100-110 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 9. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 10. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextrometholphan, eg, administration of about 30-60 mg of dextrometholphan twice daily and about 50-150 mg of (S) -bupropion twice daily. _{Upon administration, the C max of} dextrometholphan, such as standard C _max , mean C _max , central C _max , or individual C _max , was about 40-43 ng / mL, about 43-45 ng / mL, on day 11. About 40-45 ng / mL, about 45-48 ng / mL, about 48-50 ng / mL, about 45-50 ng / mL, about 50-51 ng / mL, about 51-52 ng / mL, about 52-53 ng / mL, about 53-54 ng / mL, about 54-56 ng / mL, about 50-55 ng / mL, about 55-58 ng / mL, about 58-60 ng / mL, about 55-60 ng / mL, about 60-65 ng / mL, about 65 ~ 70 ng / mL, about 70-75 ng / mL, about 75-80 ng / mL, about 80-82 ng / mL, about 82-84 ng / mL, about 84-85 ng / mL, about 80-85 ng / mL, about 85- 86 ng / mL, about 86-87 ng / mL, about 87-88 ng / mL, about 88-89 ng / mL, about 89-90 ng / mL, about 85-90 ng / mL, about 90-91 ng / mL, about 91-93 ng It can be / mL, about 93-95 ng / mL, about 90-95 ng / mL, about 95-100 ng / mL, or any C _{max in} the range between these values.

In some embodiments, a combination of (S) -bupropion and dextromethorphan, eg, administration of about 30-60 mg dextromethorphan twice daily, and about 50-150 mg (S)-twice daily. With the administration of bupropion, the FI (%) of dextromethorphan, such as standard FI (%), mean FI (%), central FI (%), or individual FI (%), is 100% on day 8. It can be less than, less than 50%, less than 40%, less than 30%, about 20-50%, about 20-40%, about 20-30%, or any FI (%) in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextromethorphan, eg, administration of about 30-60 mg of dextromethorphan daily, and administration of about 50-150 mg of (S) -bupropion twice daily. Dextromethorphan FI (%), such as standard FI (%), average FI (%), central FI (%), or individual FI (%), is less than 100%, 50 on day 9. It can be less than%, less than 40%, less than 30%, about 20-50%, about 20-40%, about 20-30%, or any FI (%) in the range between these values.

In some embodiments, a combination of (S) -bupropion and dextromethorphan, eg, administration of about 30-60 mg of dextromethorphan daily, and administration of about 50-150 mg of (S) -bupropion twice daily. Dextromethorphan FI (%), such as standard FI (%), average FI (%), central FI (%), or individual FI (%), is less than 100%, 50 on day 10. It can be less than%, less than 40%, less than 30%, about 20-50%, about 20-40%, about 20-30%, or any FI (%) in the range between these values.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Examples of neurological or central nervous system disorders that can be treated by increased bioavailability or increased plasma concentration include, but are not limited to, emotional disorders, psychiatric disorders, brain dysfunction, motor disorders, dementia, motor neuron disorders, etc. Includes neurodegenerative diseases, seizure disorders, and headaches.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Examples of emotional disorders that can be treated by increased availability or increased plasma concentration include, but are not limited to, depression, major depression, treatment-resistant depression, treatment-resistant bipolar depression, and mood circulatory disorder. Including bipolar disorder, seasonal emotional disorder, mood disorder, chronic depression (dysthymia), psychotic depression, postpartum depression, premenopausal discomfort mood disorder (PMDD), situational depression, atypical depression, Depression, anxiety disorder, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADDH), attention deficit / hyperactivity disorder (AD / HD), bipolar and manic state, obsessive disorder, hyperphagia, obesity or Includes weight gain, narcolepsy, chronic fatigue syndrome, premenopausal syndrome, addictive disorders, drug addiction or abuse, nicotine addiction, mental dysfunction, emotional dysregulation, and emotional instability.

Depression may present with depressive symptoms. These symptoms include mood changes, intense sadness, hopelessness, psychological slowdown, loss of concentration, pessimistic anxiety, impatience, anxiety, irritation, guilt, anger, worthlessness, and reckless behavior. Includes psychological changes such as suicidal ideation and attempted suicide, and / or self-deprecation. Physical symptoms of depression include insomnia, loss of appetite, loss of appetite, weight loss, weight gain, loss of vitality and libido, fatigue, restlessness, pain, distress, headache, cramps, digestive problems, and / Or circadian rhythm abnormalities of hormones are included.

Some patients may have an inadequate or no response to treatment, even after drug treatment such as antidepressants. Treatment-resistant depression (TRD), or refractory depression, is generally a symptom associated with patients who have failed treatment with at least two antidepressants. Part of the diagnosis of TRD was that patients responded poorly to treatment with antidepressants after the proper dose and course. TRD can be more difficult to treat due to comorbidities of other medical or psychological disorders such as substance / alcohol abuse or eating disorders, or misdiagnosis of TRD. Patients with TRD have insufficient response to 1, 2, 3, or more suitable antidepressant trials, or 1, 2, 3, or more prior antidepressant treatments Some patients showed a positive reaction. In some embodiments, some patients treated for treatment-resistant depression may be treated with at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more antidepressants. I'm failing.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Measures of therapeutic efficacy that can be improved by increased lucidity or increased plasma concentration include, but are not limited to, the Montgomery-Asberg Depression Rating Scale (MADRS), a brief questionnaire on quality of life and satisfaction, and features. Scope of disability tools, Sihan disability scale, patient assessment eventry for side effects (PRISE), Colombian suicide severity assessment scale (C-SSRS), brief depressant symptom scale, self-administered (QID (S) -SR), overall clinical impression Scale (CGI), Cognitive and Physical Function Questionnaire (CPFQ) at Massachusetts General Hospital, 17-item Hamilton Depression Rating Scale (HAM-D17), Questionnaire on Antidepressant Response at Massachusetts General Hospital (MGH ATRQ), 16-item self-administered brief depressant symptom scale (QID (S) -SR16), Sihan disability scale (SDS), severity clinical general impression scale (CGI-S), impression evaluation of changes due to treatment (CGI-C) , EuroQOL5 viewpoint 5 stages (EQ-5D-5L), patient's general impression of change (PGIC), 7 items of generalized anxiety disorder (GAD-7), improvement general impression scale (CGI-I), Shihan Disability Scale (SDS), 16-item Self-filling Brief Psychiatric Symptom Scale (QID (S) -SR16), Hamilton Anxiety Scale (HAM-A), Cognitive and Physical Function Questionnaire (CPFQ), CPQF -Recognition subscales (items 4-7), Brief Psychiatric Symptoms Rating Scale (BPRS), Number Code Substitution Test (DSST), Ray's Auditory Language Learning Test (RAVLT), Trailmaking Test (TMT), Stroop Color Naming test (STROOP), simple reaction time (SRT), selective reaction time, etc.

Patients who can benefit from the treatments described herein include patients under about 18 years, about 0-5 years, about 5-10 years, about 10-12 years, or about 12-18 years. Pediatric patients such as, about 18-65 years old, about 18-30 years old, about 30-50 years old, about 50-65 years old, and other adult patients, and over 65 years old, about 65-75 years old, 75-90 years old. Includes elderly patients, such as those aged or over 90 years.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or dextromethorphan biology Treatment of TRD by increased bioavailability or increased plasma concentration causes depressive symptoms at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least. It can result in a reduction of about 60%, at least about 70%, at least about 80%, at least about 90%, about 100% reduction, or any percentage reduction between any of these values.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or schizophrenia biology Mental disorders that can be treated by increased utilization or increased plasma concentration are, but are not limited to, schizophrenia, general anxiety disorder, social anxiety disorder, panic disorder, mania, compulsive disorder, post-psychotrauma. Anxiety disorders such as stress disorder (PTSD); mania, manic depression, mild mania, unipolar depression, depression, stress disorder, physical expression disorder, personality disorder, psychiatric disorder, schizophrenia, delusional disorder, schizophrenia Includes emotional disorders, schizophrenia tendencies, aggression, aggression in Alzheimer's disease, excitement, and excitement in Alzheimer's disease.

The excitement associated with Alzheimer's disease occurs as the disease progresses. The feeling of impatience itself can manifest itself as inappropriate language, emotions, and / or physical behavior. Inappropriate behavior, but not limited to, irritability, inappropriate emotional reactions, demands for attention, threats, irritation, frustration, screaming, repeated questions, mood swings, taunts, rants, physical outbursts, emotional Pain, restlessness, shredding, sleep disorders, delusions, illusions, pacing, wandering, exploration, hunting, repetitive body movements, stocking, shadowing, beatings, scratches, bites, combativeness, hyperactivity, and / Or may include kicking.

In some embodiments, increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / Alternatively, treatment of excitement associated with Alzheimer's disease by increasing bioavailability of dextromethorphan or increasing plasma concentration may result in at least 5%, at least about 10%, at least about 20%, at least about 20% of the symptoms associated with excitement. 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, about 100% reduction, or any percentage between any of these values Can result in a decrease in plasma.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan A measure of the therapeutic effect of excitement that can be ameliorated by increased utilization or increased plasma concentration is, but is not limited to, all items of the Neuropsychiatric Inventory Clinician (NPI-C) Rating Scale, Neuropsychiatry. Inventory Clinician (NPI-C) Rating Scale Excitement Item, Cohen Mansfield Excitement Assessment Sheet (CMAI), Cornell Dementia Dementia Depression Scale (CSDD), Neuropsychiatric Symptom Assessment (NPI Excitement / Aggression Item), Combined Drugs (frequency of concomitant drug use), evaluation of activities of daily living (ADC (S) -ADL) in Alzheimer's disease joint research, individual items of neuropsychiatric symptom evaluation (NPI), and items of indifference of NIP-C, NPI Excitement / aggression, total NPI score including caregiver burden (range 0-144), excitement of impression of clinical overall change in modified Alzheimer's disease collaboration (mADC (S) -CGIC excitement), for change Patient's general impression (PGIC) (caregiver's evaluation), dementia QOL (DEMQOL), Alzheimer's disease QOL scale (QoL-AD), Zarit care burden scale, medical resource utilization in dementia (RUD), Alzheimer's Individual items of cognitive function subscale (ADA (S) -Cog) to evaluate cognitive dysfunction of disease, minimal state test (MMSE), caregiver burden index (CSI), neuropsychiatric symptom evaluation (NPI), neuropsychiatric The total symptom evaluation (NPI) score, neuropsychiatric symptom evaluation (NPI excitement / aggression item), neuropsychiatric symptom evaluation (NPI caregiver burden item), etc. may be included.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or dextromethorphan biology Drug addiction that can be treated by increased availability or increased plasma concentration is not limited to drug addiction, cocaine addiction, psychostimulants (eg, cracks, cocaine, speed, females), nicotine, alcohol, opioids. Includes, antidepressants and hypnotics, cannabis (marijuana), amphetamines, hallucinogens, fencyclidine, volatile solvents, and volatile nitrites. Nicotine addiction includes all known forms of nicotine addiction, including tobacco smoking, cigar and / or pipe, e-cigarette, and chewing tobacco addiction.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Brain dysfunction that can be treated by increased utilization or increased plasma concentration is not limited to, but is limited to senile dementia, Alzheimer's dementia, amnesia, amnesia / amnesia syndrome, epilepsy, impaired consciousness, coma, Includes disorders with intellectual disabilities such as decreased attention, speech disorders, voice spasms, Parkinson's disease, Lennox-Gastaut syndrome, autism, hyperactivity syndrome, and schizophrenia. Brain dysfunction also includes, but is not limited to, stroke, cerebral infarction, cerebral hemorrhage, cerebral arteriosclerosis, cerebrovascular thrombosis, head trauma, and impaired consciousness, senile dementia, coma, diminished attention, and speech disorders. It also includes disorders caused by symptomatic cerebrovascular accidents.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Movement disorders that can be treated by increased availability or increased plasma concentration include, but are not limited to, acacia, akinesia, related exercise, atetosis, restless legs, restless legs syndrome, restless legs syndrome, slow motion, cerebral paralysis, chorea, huntington's disease. , Rheumatic chorea, Sidenum chorea, dyskinesia, delayed dyskinesia, dystonia, eyelid spasm, spastic oblique neck, dopamine-reactive dystonia, Parkinson's disease, lower limb restless legs syndrome (RLS), tremor, essential tremor, Includes Tourette's syndrome and Wilson's disease.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Dementia that can be treated by increased utilization or increased plasma concentration is, but is not limited to, Alzheimer's disease, Parkinson's disease, vascular dementia, Levy body dementia, mixed dementia, frontotemporal dementia. Dementia, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, Huntington's disease, Wernicke-Korsakov syndrome, Pick's disease.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Motor neuron diseases that can be treated by increased availability or increased plasma concentration include, but are not limited to, amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis, primary lateral sclerosis (PLS), Includes progressive amyotrophic atrophy, post-polio syndrome (PPS), spinal muscular atrophy (SMA), spinal muscular atrophy, Tay-Sachs disease, Sandhoff's disease, and hereditary spastic paralysis.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Neurodegenerative diseases that can be treated by increased utilization or increased plasma concentration are, but are not limited to, Alzheimer's disease, prion-related diseases, cerebral atrophy, spinal muscular atrophy (SCA), spinal muscular atrophy (SMA). , Spinal muscular atrophy, Friedrich's atrophy, Huntington's disease, Levy's body disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), multiple sclerosis (MS), multiple system atrophy Symptoms, Shy-Drager syndrome, cortical basal nuclear degeneration, progressive supranuclear palsy, Wilson's disease, Menkes' disease, adrenal leukodystrophy, autosomal dominant cerebral atrophy with subcortical infarction and leukoencephalopathy (CADASIL), muscular dystrophy, Charcot Includes Marie-Tooth disease (CMT), familial spastic antiparalysis, neurofibromatosis, Olive bridge cerebral atrophy or degeneration, amyotrophic lateral degeneration, Gillan Valley syndrome, and spastic antiparalysis.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dexstrometolphan Seizure disorders that can be treated by increased availability or increased plasma concentration include, but are not limited to, non-seizure, epilepsy, febrile seizures; simple partial epilepsy, Jackson seizures, complex partial epilepsy, and persistent partial epilepsy. Focal epilepsy including, but not limited to, generalized tonic interstitial seizures, diabetic seizures, weakness seizures, myoclonic seizures, juvenile myoclonic seizures, and generalized seizures including but not limited to febrile seizures; and seizures Includes overlap.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Types of headaches that can be treated by increased bioavailability or increased plasma concentration include, but are not limited to, migraine headaches, tension-type headaches, and swarm headaches.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Other neuropathy that can be treated by increased availability or increased plasma concentration include let syndrome, autism, ringing in the ears, consciousness disorder, sexual dysfunction, refractory cough, narcolepsy, cataplexy; abductor muscle spasms. Sexual dysfunction, adduction muscle spasmodic dysfunction, myotonic dysphonia, and dysphonia due to uncontrolled laryngeal muscle spasm, including but not limited to tremor; diabetic dysfunction, methotrexate neurotoxicity, etc. Chemotherapy-induced neurotoxicity; incontinence including, but not limited to, stress urinary incontinence, urgency urinary incontinence, and stool incontinence; and erectile dysfunction.

In some embodiments, increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / Or increased bioavailability or increased plasma concentration of dextromethorphan may result in pain, joint pain, pain associated with sickle erythema, affective dysregulation, depression (including refractory depression), memory and It can be used for the treatment of cognitive disorders, schizophrenia, Parkinson's disease, muscular atrophic lateral sclerosis (ALS), Let's syndrome, seizures, cough (including chronic cough) and the like.

In some embodiments, increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / Alternatively, increased bioavailability or increased plasma concentration of dextromethorphan can be used for the treatment of refractory depression.

Increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / or biology of dextrometholphan Increased utilization or increased plasma concentration includes musculoskeletal pain, neuropathy pain, cancer-related pain, acute pain, nociceptive pain, inflammatory pain, arthritis pain, complex local pain syndrome, etc. It can be used to treat or relieve any type of pain, including but not limited to these.

In some embodiments, increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / Alternatively, increased bioavailability or increased plasma concentration of dextromethorphan may be useful in alleviating neuropathic pain.

Examples of neuropathic pain include diabetic peripheral neuropathy, postherpetic neuralgia, trigeminal neuralgia, monoradiculopathies, phantom limb pain, central pain and the like. Other causes of neuropathic pain include cancer-related pain, lumbar radiculopathy, spinal cord injury, post-stroke pain, central multiple sclerosis pain, HIV-related neuropathy, and radiation therapy or chemotherapy. Includes related neuropathy and the like.

In some embodiments, increased bioavailability or plasma concentration of (S) -bupropion, increased bioavailability or plasma concentration of (R, R) -hydroxybupropion, and / Alternatively, increased bioavailability or increased plasma concentration of dextromethorphan is administered to relieve fibromyalgia.

Adverse events associated with bupropion or dextromethorphan that can be avoided or reduced by the methods described herein are associated with adverse events of the central nervous system, gastrointestinal events, or any of these compounds. Includes another type of adverse event. Negative events of the central nervous system (CNS) include, but are not limited to, tension, dizziness, insomnia, drowsiness, tremor, illusion, spasm, CNS depression, fear, anxiety, headache, increased irritability or agitation, ear ringing. , Dizziness, dizziness, sedation, somnolence, confusion, misunderstanding, malaise, coordination disorder, fatigue, euphoria, irritability, insomnia, sleep disorder, spasm attack, excitement, tension, hystery, illusion, delusion, Includes eccentricity, headache and / or migraine, and extrapyramidal symptoms such as gaze attacks, somnolence, hyperexcitability, hypertonia, insomnia and / or tongue protrusion.

Adverse events of the digestive system include, but are not limited to, nausea, vomiting, abdominal pain, swallowing disorders, dyspepsia, diarrhea, abdominal bloating, intestines, peptic ulcer with bleeding, loose stools, constipation, stomach pain, heartburn, gas, Includes loss of appetite, stomach fullness, dyspepsia, abdominal bloating, gastric hyperacidity, dry mouth, gastrointestinal disorders, and stomach pain.

Other adverse events that can be reduced or avoided by the methods described herein include dysmenorrhea of rotation and movement, agitation, weakness of the arms, bloating, hazy eyes, burning eyes, ringing in the ears, vital signs. Changes (including, but not limited to, heart rate, respiratory rate, body temperature, blood pressure), coldness, constipation, difficulty concentrating, poor sleep, difficulty falling asleep, difficulty urinating, difficulty stooling, discomfort in the ears , Eye discomfort, stomach discomfort, dizziness, dry lips, dry mouth, dry throat, dysmenorrhea, fatigue, feverish, heavy head, more excited than usual, tired than usual Fatigue, tremor of hands, weakness of hands, headache, chest burn, burning, increased blood pressure, sensitive skin, sensitive head and face skin, involuntary muscle contraction, involuntary muscles of the whole body Contraction, knee pain, weakness in the legs, stunned stools, loose stools, loss of appetite, lower back pain, dysmenorrhea, metallic taste, more saliva than usual, dry mucous membrane, stuffy nose, nausea, nasal discharge, light pressure on the eyes Tremor, stretch or tremor, skin hypersensitivity, skin hypersensitivity of arms, face, and / or head, sleep disorders, loose stools, stomach pain, stomach discomfort, sweating of hands and / or feet, throat inflammation Includes sore throat, ringing in the ears, tremors, and / or weakness. Any of these side effects may be referenced or grouped according to the corresponding term, equivalent term, or other related term found in the MedRA.

The term "treat" or "treat" refers to any diagnosis, treatment, alleviation, treatment, or prevention of a human or other animal disease, or any effect on the structure or any function of the human or other animal's body. Activities are included.

Patients who can benefit from the treatments described herein are about less than 18 years old, about 0-5 years old, about 5-10 years old, about 10-12 years old, or about 12-18 years old. Pediatric patients such as patients, adult patients such as about 18-65 years old, about 18-30 years old, about 30-50 years old, about 50-65 years old, 65 years old and over, about 65-75 years old, about 75-90 years old Includes elderly patients, such as those aged 90 or older.

"Compositions and methods for increasing the metabolic lifespan of dextrometholphan, and related agents, filed on July 10, 2017 under Application No. 15 / 645,939 and registered on January 16, 2018. US Pat. No. 9,867,819, US Pat. No. 9,867,819, entitled "Pharmacodynamic Effects," is incorporated herein by reference in its entirety. In particular, the amounts and dosing regimens described for bupropion described in US Pat. No. 9,867,819 are described herein as (S) -bupropion or (R) -bupropion. Can be applied to. In addition, the amounts and dosing regimens of dextromethorphan described in US Pat. No. 9,867,819 can be applied herein. In addition, conditions that can be treated with the dosage forms described in US Pat. No. 9,867,819 can also be treated in a similar manner using the dosage forms and methods described herein. ..

The following embodiments can be considered.
Embodiment 1.
Plasma bupropion or metabolites thereof, comprising orally administering to humans at least once daily a dosage form containing at least 95% enantiomerically pure about 50 mg to about 100 mg (S) -bupropion. Method of delivery.

Embodiment 2.
To select human patients who require a pharmacokinetic profile obtained by orally administering a reference dosage form containing a first amount of racemic bupropion at a first frequency of administration.
A dosage form containing a second amount of (S) -bupropion that is at least 95% enantiomerically pure is orally administered at the first dose frequency and the reference dosage form is administered at the first dose frequency. To achieve the same pharmacokinetic profile achieved by administration,
Including
The first administration frequency is once a day or twice a day.
The second amount is about 40% to about 60% of the first amount.
A method of delivering bupropion to human plasma.

Embodiment 3.
To select human patients with a condition that can be treated by oral administration of a reference dosage form containing a first amount of racemic bupropion at the first frequency of administration.
A dosage form containing a second amount of (S) -bupropion that is at least 95% enantiomerically pure is orally administered at the first dose frequency and the reference dosage form is administered at the first dose frequency. To achieve the same therapeutic effect as achieved by administration,
Including
The first administration frequency is once a day or twice a day.
The second amount is about 40% to about 60% of the first amount.
A method of treating a condition that can be treated with racemic bupropion.

Embodiment 4.
The method of embodiment 1, wherein the human is in need of treatment with (S) -bupropion.

Embodiment 5.
(S) -The method of embodiment 1, 2, 3 or 4, wherein _{the C max of bupropion is at least about 60 ng / mL.}

Embodiment 6.
The first embodiment, which has the effect of increasing _{the C max} of (S) -bupropion _{by at least 5 times as compared with the C max} of (R) -bupropion when the same amount of (R) -bupropion is administered to humans. The method according to 2, 3, 4, or 5.

Embodiment 7.
The method according to embodiment 1, 2, 3, 4, 5, or 6, _{wherein the C max} of (R, R) -hydroxybupropion in the human is at least about 500 ng / mL.

Embodiment 8.
_{The effect of increasing the C min} of (R, R) -hydroxybupropion by at least 3 times as _{compared with the C min} of (R, R) -hydroxybupropion when the same amount of (R) -bupropion was administered to the human. The method according to embodiment 1, 2, 3, 4, 5, 6, or 7.

Embodiment 9.
The method according to embodiment 1, 2, 3, 4, 5, 6, 7, or 8, wherein the dosage form is administered once daily.

Embodiment 10.
The method according to embodiment 1, 2, 3, 4, 5, 6, 7, or 8, wherein the dosage form is administered twice daily.

Embodiment 11.
Embodiments 1, 2, where (R, R) -hydroxybupropion is at least 97% of the total amount of (R, R) -hydroxybupropion and (S, S) -hydroxybupropion present in the human plasma. 3, 4, 5, 6, 7, 8, 9, or 10.

Embodiment 12.
The method according to embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11, which has the effect of providing a therapeutically effective plasma concentration of (R, R) -hydroxybupropion. ..

Embodiment 13.
(S) -The method according to embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, which has the effect of providing a therapeutically effective plasma concentration of bupropion.

Embodiment 14.
The method according to embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, wherein the human is in need of treatment with (R, R) -hydroxybupropion.

Embodiment 15.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 such that _{the C max} of (R, R) -hydroxybupropion in the human is at least about 500 ng / mL. , Or the method according to 14.

Embodiment 16.
13. The method of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, wherein the dosage form is administered for at least consecutive 8 days.

Embodiment 17.
16. The method of embodiment 16, wherein the dosage form is administered for at least 14 consecutive days.

Embodiment 18.
16. The method of embodiment 16, wherein the dosage form is administered for at least 21 consecutive days.

Embodiment 19.
Embodiments 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15, wherein the dosage form contains from about 60 mg to about 90 mg of (S) -bupropion. , 16, 17 or 18.

20.
The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 in which the dosage form is administered once, at least for the next consecutive 4-7 days. , 16, 17, 18, or 19.

21.
The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 in which the dosage form is administered once, at least for the next seven consecutive days. , 17, 18, 19, or 20.

Embodiment 22.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, wherein the dosage form contains from about 70 mg to about 80 mg of the (S) -bupropion. 15, 16, 17, 18, 19, 20, or 21.

23.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, where _{the C max} of (S) -bupropion in the human is at least about 70 ng / mL. 15, 16, 17, 18, 19, 20, 21, or 22.

Embodiment 24.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, _12, where the AUC 0-12 of (S) -bupropion in the human is at least about 400 ng · hr / mL, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23.

Embodiment 25.
_{The method of embodiment 24, wherein the AUC 0-12} of (S) -bupropion in the human is at least about 500 ng · hr / mL to about 900 ng · hr / mL.

Embodiment 26.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 where the dosage form slowly releases the (S) -bupropion. , 18, 19, 20, 21, 22, 23, 24, or 25.

Embodiment 27.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, where the dosage form further contains dextromethorphan, 19, 20, 21, 22, 23, 24, 25, or 26.

Embodiment 28.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, wherein the dosage form contains from about 70 mg to about 80 mg of the (S) -bupropion. 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27.

Embodiment 29.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 such that _{the C max} of (R, R) -hydroxybupropion in the human is at least about 600 ng / mL. , 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28.

Embodiment 30.
Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 such that _{the AUC 0-12} of (R, R) -hydroxybupropion in the human is at least about 7000 ng · hr / mL. , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29.

Embodiment 31.
_{30. The method of embodiment 30, wherein the AUC 0-12} of (R, R) -hydroxybupropion in the human is at least about 8000 ng · hr / mL.

Embodiment 32.
For humans requiring treatment with dextromethorphan and at least about 90 mg of at least 95% microscopically pure (S) -bupropion at least once daily with both (S) -bupropion and dextromethorphan. _{The C max} of (S) -bupropion in the human, including co-administration, was at least about 90 ng / mL, and that of (R) -bupropion when the same amount of (R) -bupropion was administered to the human. compared to C _max, (S) - it has the effect of increasing at least 3-fold the C _max of bupropion, (S) - method of increasing the plasma concentrations of bupropion and dextromethorphan.

Embodiment 33.
32. The method of embodiment 32, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days.

Embodiment 34.
32. The method of embodiment 32, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 14 consecutive days.

Embodiment 35.
32. The method of embodiment 32, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form.

Embodiment 36.
The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 33, 34, or 35. The method of embodiment 33, 34, or 35, wherein the dosage form is administered once, at least for the next consecutive 4-7 days.

Embodiment 37.
The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 33, 34, or 35. The method of embodiment 33, 34, or 35, wherein the dosage form is administered once, at least for the next 7 consecutive days.

Embodiment 38.
32, 33, 34, 35, 36, or 37 of embodiments 32, 33, 34, 35, 36, or 37, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion.

Embodiment 39.
13. The method of embodiment 32, 33, 34, 35, 36, 37 or 38, _{wherein the C max} of (S) -bupropion in the human is at least about 110 ng / mL.

Embodiment 40.
32, 33, 34, 35, 36, 37, 38 or 39 of embodiments 32, 33, 34, 35, 36, 37, 38 or 39, _{wherein the AUC 0-12} of (S) -bupropion in the human is at least about 800 ng · hr / mL.

Embodiment 41.
The method according to embodiment 32, 33, 34, 35, 36, 37, 38, 39 or 40, wherein the (S) -bupropion is administered in a dosage form that sustained the release of the (S) -bupropion.

Embodiment 42.
Requires treatment with dextromethorphan and at least about 90 mg of at least 95% microscopically pure (S) -bupropion at least once daily with both (R, R) -hydroxybupropion and dextromethorphan. _{In the case where the C max} of (R, R) -hydroxybupropion in the human is at least about 700 ng / mL and the same amount of (R) -bupropion is administered to the human. _{The effect of increasing the C max} of (R, R) -hydroxybupropion by at least 3-fold compared to the C _{max of} (R, R) -hydroxybupropion, of (R, R) -hydroxybupropion and dextromethorphan A method of increasing plasma concentration.

Embodiment 43.
42. The method of embodiment 42, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days.

Embodiment 44.
42. The method of embodiment 42, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least two consecutive 21 days.

Embodiment 45.
42. The method of embodiment 42, 43, or 44, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form.

Embodiment 46.
The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 42. The method of embodiment 42, 43, 44, or 45, wherein the dosage form is administered once, at least for the next consecutive 4-7 days.

Embodiment 47.
The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 42. The method of embodiment 42, 43, 44, 45, or 46, wherein the dosage form is administered once, at least for the next 7 consecutive days.

Embodiment 48.
42, 43, 44, 45, 46, or 47, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion.

Embodiment 49.
42, 43, 44, 45, 46, 47, or 48 of embodiments 42, 43, 44, 45, 46, 47, or 48, _{wherein the C max} of (R, R) -hydroxybupropion in the human is at least about 900 ng / mL.

Embodiment 50.
42, 43, 44, 45, 46, 47, 48, or 49, _{wherein the AUC 0-12} of (R, R) -hydroxybupropion in the human is at least about 10,000 ng · hr / mL. Method.

Embodiment 51.
The method according to embodiment 42, 43, 44, 45, 46, 47, 48, 49, or 50, wherein the (S) -bupropion is administered in a dosage form that sustained the release of the (S) -bupropion.

Embodiment 52.
At least once daily, comprising orally administering at least about 90 mg of at least about 95% microscopically pure (S) -bupropion to a person in need of treatment with (S) -bupropion, said person. _{The C min} of (S) -bupropion in (S) was at least about 20 ng / mL, as compared with _{the C min} of (R) -bupropion when a dosage form containing the same amount of (R) -bupropion was administered to the human. , (S) -A method of increasing the plasma concentration of bupropion, which has the effect of increasing _{the C min of (S) -bupropion by at least 3-fold.}

Embodiment 53.
52. The method of embodiment 52, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days.

Embodiment 54.
52. The method of embodiment 52, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 14 consecutive days.

Embodiment 55.
58. The method of embodiment 52, 53, or 54, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form.

Embodiment 56.
The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 58. The method of embodiment 52, 53, 54, or 55, wherein the dosage form is administered once, at least for the next consecutive 4-7 days.

Embodiment 57.
The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 58. The method of embodiment 52, 53, 54, 55, or 56, wherein the dosage form is administered once, at least for the next 7 consecutive days.

Embodiment 58.
52, 53, 54, 55, 56, or 57 of embodiments, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion.

Embodiment 59.
58. The method of embodiment 52, 53, 54, 55, 56, 57, or 58, _{wherein the C max} of (S) -bupropion in the human is at least about 110 ng / mL.

Embodiment 60.
52, 53, 54, 55, 56, 57, 58, or 59 of embodiments 52, 53, 54, 55, 56, 57, 58, or 59, _{wherein the AUC 0-12} of (S) -bupropion in the human is at least about 800 ng · hr / mL.

Embodiment 61.
52, 53, 54, 55, 56, 57, 58, 59 or 60 of embodiments 52, 53, 54, 55, 56, 57, 58, 59 or 60, wherein the (S) -bupropion is administered in a dosage form that sustained the release of the (S) -bupropion.

Embodiment 62.
Includes oral administration of at least about 90 mg of at least 95% mirror isomerically pure (S) -bupropion at least once daily to humans in need of treatment with (R, R) -hydroxybupropion. , in the human (R, R) - _{C min} of at least about 700 ng / mL next hydroxy bupropion, the same amount of (R) - bupropion and when administered to the human (R, R) - hydroxy bupropion _{C min} A method of increasing the plasma concentration of (R, R) -hydroxybupropion, which has the effect of increasing _{the C min} of (R, R) -hydroxybupropion by at least 3-fold as compared to.

Embodiment 63.
62. The method of embodiment 62, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days.

Embodiment 64.
62. The method of embodiment 62, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least two consecutive 21 days.

Embodiment 65.
62, 63, or 64, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form.

Embodiment 66.
The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 62, 63, 64, or 65, wherein the dosage form is administered once, at least for the next consecutive 4-7 days.

Embodiment 67.
The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 62, 63, 64, 65 or 66, wherein the dosage form is administered once, at least for the next 7 consecutive days.

Embodiment 68.
The method of embodiment 62, 63, 64, 65, 66 or 67, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion.

Embodiment 69.
62, 63, 64, 65, 66, 67, or 68 of embodiments 62, 63, 64, 65, 66, 67, or 68, _{wherein the C max} of (R, R) -hydroxybupropion in the human is at least about 900 ng / mL.

Embodiment 70.
62, 63, 64, 65, 66, 67, 68, or 69, _{wherein the AUC 0-12} of (R, R) -hydroxybupropion in the human is at least about 10,000 ng · hr / mL. Method.

Embodiment 71.
The method according to embodiment 62, 63, 64, 65, 66, 67, 68, 69, or 70, wherein the (S) -bupropion is administered in a dosage form that sustained the release of the (S) -bupropion.

Embodiment 72.
A method of treating central nervous system (CNS) disorders in humans, in which a therapeutically effective amount of at least about 95% enantiomerically pure (S) -bupropion-containing dosage form and dextromethorphan is administered to humans. Methods, including treating CNS disorders.

Embodiment 73.
72. The method of embodiment 72, wherein the CNS disorder includes depression.

Embodiment 74.
28. The method of embodiment 72, wherein the CNS disorder comprises treatment-resistant depression.

Embodiment 75.
72. The method of embodiment 72, wherein the CNS disorder includes an addictive disorder.

Embodiment 76.
72. The method of embodiment 72, wherein the CNS disorder comprises nicotine addiction.

Embodiment 77.
72. The method of embodiment 72, wherein the CNS disorder comprises alcoholism.

Embodiment 78.
The method of embodiment 72, wherein the CNS disorder includes Alzheimer's disease.

Embodiment 79.
28. The method of embodiment 72, 73, 74, 75, 76, 77, or 78, wherein the dosage form is a tablet, capsule, or syrup.

80.
28. The method of embodiment 72, 73, 74, 75, 76, 77, 78, or 79, wherein the dosage form is orally administered to the human.

Embodiment 81.
28. The method of embodiment 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the dosage form is orally administered to the human daily.

Embodiment 82.
28. The method of embodiment 72, 73, 74, 75, 76, 77, 78, 79, 80, or 81, wherein the dosage form is orally administered to the human once daily.

Embodiment 83.
28. The method of embodiment 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, or 82, wherein the dosage form is orally administered to the human twice daily.

Embodiment 84.
28. The method of embodiment 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, or 83, wherein the dosage form is orally administered to the human under fasting conditions.

Embodiment 85.
28. The method of embodiment 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, or 84, wherein the dosage form is orally administered to the human daily for at least 8 consecutive days.

Embodiment 86.
Embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, or 85, wherein the dosage form contains from about 100 mg to about 200 mg of the (S) -bupropion. The method described in.

Embodiment 87.
Embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, wherein the dosage form contains from about 104 mg to about 106 mg of the (S) -bupropion. Or the method according to 86.

Embodiment 88.
Embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, wherein the dosage form contains from about 148 mg to about 152 mg of the (S) -bupropion. 86, or 87.

Embodiment 89.
Embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, wherein both the (S) -bupropion and the dextromethorphan are included in the dosage form. 85, 86, 87, or 88.

Embodiment 90.
Embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, wherein the dosage form contains from about 10 mg to about 50 mg of the dextromethorphan. 87, 88, or 89.

Embodiment 91.
Embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, wherein the dosage form contains from about 44 mg to about 46 mg of the dextromethorphan. 87, 88, 89, or 90.

Embodiment 92.
The dosage forms are well tolerated, embodiments 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, or 91.

Embodiment 93.
Of dextromethorphan, including administration of a therapeutically effective amount of a dosage form and dextromethorphan containing at least about 95% enantiomerically pure (S) -bupropion to humans in need of treatment with bupropion. A method of increasing the plasma concentration of (S) -bupropion while increasing the plasma concentration.

Embodiment 94.
The method according to embodiment 93, which has the effect of increasing _{the C max} of (S) -bupropion as compared to the administration of the same amount of racemic bupropion.

Embodiment 95.
(S) - the C _max of bupropion, the same amount of (R) - a dosage form comprising bupropion when administered to said human (R) - there are at least 3 times higher that the effect of the C _max of bupropion, implementation The method according to form 93 or 94.

Embodiment 96.
_13. The method of embodiment 93, 94, or 95, which has the effect of increasing AUC 0-12 of (S) -bupropion as compared to administration of the same amount of racemic bupropion.

Embodiment 97.
(S) - the _{AUC 0-12} of bupropion, the same amount of (R) - a dosage form comprising bupropion when administered to the human (R) - at least 3 times higher that the effect of bupropion _{AUC 0-12} The method according to embodiment 96.

Embodiment 98.
28. The method of embodiment 95, 96, or 97, wherein the dosage form is administered at least once daily for at least consecutive 8 days.

Embodiment 99.
The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 35. The method of embodiment 95, 96, 97, or 98, wherein the dosage form is administered once, at least for the next consecutive 4-7 days.

Embodiment 100.
The method of embodiment 95, 96, 97, 98, or 99, wherein the dosage form is well tolerated.

Embodiment 101.
A dosage form containing at least about 95% mirror image of isomerically pure (R) -bupropion and dextromethorphan, which can be administered orally to humans in equal amounts of (S) -bupropion and dextromethorphan. A dosage form capable of increasing the plasma concentration of dextromethorphan in the human as compared to oral administration of a reference dosage form containing the same amount of dextromethorphan.

Embodiment 102.
The dosage form according to embodiment 101, which comprises from about 100 mg to about 200 mg of (R) -bupropion.

Embodiment 103.
The dosage form according to embodiment 102, which comprises from about 104 mg to about 106 mg of (R) -bupropion.

Embodiment 104.
The dosage form of embodiment 102, comprising from about 148 mg to about 152 mg of (R) -bupropion.

Embodiment 105.
The dosage form according to embodiment 101, 102, 103, or 104, which comprises from about 10 mg to about 50 mg of dextromethorphan.

Embodiment 106.
The dosage form according to embodiment 105, which comprises from about 44 mg to about 46 mg of dextromethorphan.

Embodiment 107.
The dosage form according to embodiment 101, which comprises from about 100 mg to about 110 mg (R) -bupropion and from about 40 mg to about 50 mg dextromethorphan.

Embodiment 108.
The dosage form according to embodiment 101, 102, 103, 104, 105, 106, or 107, which is orally administered to the human daily.

Embodiment 109.
The dosage form according to embodiment 101, 102, 103, 104, 105, 106, 107, or 108, which is orally administered to the human once daily.

Embodiment 110.
The dosage form according to embodiment 101, 102, 103, 104, 105, 106, 107, or 108, which is orally administered to the human twice daily.

Embodiment 111.
The dosage form according to embodiment 109 or 110, which is orally administered to the human daily for at least 8 consecutive days.

Embodiment 112.
The dosage form according to embodiment 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, or 111, which is orally administered to the human under fasting conditions.

Embodiment 113.
_{The dosage form of embodiment 111, wherein the C max} of dextromethorphan in the human is at least about 80 ng / mL on the 8th day of daily oral administration of the dosage form for 8 consecutive days.

Embodiment 114.
The dosage form according to embodiment 113, which is in the form of a syrup, tablet, capsule, spray, or troche.

Embodiment 115.
The dosage form according to embodiment 113 or 114, which is used to treat a neuropsychiatric disorder in the human in need of treatment.

Embodiment 116.
Embodiments 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, which are used to treat a cold or cough in the human in need of treatment. Alternatively, the dosage form according to 115.

Embodiment 117.
Embodiments 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, or 115, which are used to relieve pain in the human in need of relief. Dosage form described in.

Embodiment 118.
Embodiments 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, or 115, used to treat addiction in humans in need of treatment. Dosage form described in.

Embodiment 119.
Embodiments 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, which are well tolerated when administered to the human. , Or the dosage form according to 118.

Embodiment 120.
Containing the administration of a dosage form to humans containing at least about 95% enantiomerically pure (R) -bupropion and dextromethorphan, depending on the dosage form, the same amount of (S) -bupropion and the same amount. A method for increasing the plasma concentration of dextromethorphan in humans, which is capable of increasing the plasma concentration of dextromethorphan in the human as compared to a reference dosage form containing dextromethorphan.

Embodiment 121.
120. The method of embodiment 120, wherein the dosage form contains from about 100 mg to about 200 mg of (R) -bupropion.

Embodiment 122.
120. The method of embodiment 120, wherein the dosage form contains from about 100 mg to about 110 mg of (R) -bupropion.

Embodiment 123.
120. The method of embodiment 120, wherein the dosage form contains from about 148 mg to about 152 mg of (R) -bupropion.

Embodiment 124.
The method of embodiment 120, 121, 122, or 123, wherein the dosage form contains from about 10 mg to about 50 mg dextromethorphan.

Embodiment 125.
The method of embodiment 124, wherein the dosage form contains from about 40 mg to about 50 mg of dextromethorphan.

Embodiment 126.
12. The method of embodiment 125, wherein the dosage form contains from about 100 mg to about 110 mg (R) -bupropion and from about 40 mg to about 50 mg dextromethorphan.

Embodiment 127.
12. The method of embodiment 120, 121, 122, 123, 124, 125, or 126, wherein the dosage form is orally administered to the human under fasting conditions.

Embodiment 128.
12. The method of embodiment 120, 121, 122, 123, 124, 125, 126, or 127, wherein the dosage form is well tolerated.

Embodiment 129.
A method of treating central nervous system (CNS) disorders in humans, in which a dosage form containing at least about 95% enantiomerically pure (S) -bupropion of a therapeutically effective amount is administered to humans for CNS disorders. The method comprising treating the human being not administered dextromethorphan.

Embodiment 130.
129. The method of embodiment 129, wherein the CNS disorder includes depression.

Embodiment 131.
129 or 130 of the method of embodiment 129 or 130, wherein the CNS disorder comprises treatment-resistant depression.

Embodiment 132.
129, 130, or 131. The method of embodiment 129, 130, or 131, wherein the CNS disorder is an addictive disorder.

Embodiment 133.
The method of embodiment 132, wherein the CNS disorder is nicotine addiction.

Embodiment 134.
The method of embodiment 132, wherein the CNS disorder is alcoholism.

Embodiment 135.

The method of embodiment 132, wherein the CNS disorder is Alzheimer's disease.
Embodiment 136.
129, 130, 131, 132, 133, 134, or 135, wherein the dosage form contains no active agent other than (S) -bupropion.

Embodiment 137.
The method according to embodiment 129, 130, 131, 132, 133, 134, or 135, wherein the dosage form contains less than 0.1% of the active agent in addition to (S) -bupropion.

Embodiment 138.
129, 130, 131, 132, 133, 134, 135, 136, or 137, wherein the dosage form is in the form of tablets, capsules, or syrups.

Embodiment 139.
129, 130, 131, 132, 133, 134, 135, 136, 137, or 138, wherein the dosage form is orally administered to the human daily.

Embodiment 140.
139. The method of embodiment 139, wherein the dosage form is orally administered to the human once daily.

Embodiment 141.
139. The method of embodiment 139, wherein the dosage form is orally administered to the human twice daily.

Embodiment 142.
129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, or 141, wherein the dosage form is orally administered to the human under fasting conditions.

Embodiment 143.
129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, or 142, wherein the dosage form is orally administered to the human daily for at least 8 consecutive days. the method of.

Embodiment 144.
Embodiments 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, or, wherein the dosage form contains from about 100 mg to about 200 mg of (S) -bupropion. 143.

Embodiment 145.
The method of embodiment 144, wherein the dosage form contains from about 104 mg to about 106 mg of (S) -bupropion.

Embodiment 146.
14. The method of embodiment 144, wherein the dosage form contains from about 148 mg to about 152 mg of (S) -bupropion.

Embodiment 147.
Plasma concentration of (S) -bupropion, comprising administering to a human in need of treatment with bupropion a dosage form containing at least about 95% enantiomerically pure (S) -bupropion of a therapeutically effective amount. A method in which the dosage form does not contain dextromethorphan.

Embodiment 148.
(S) -The method of embodiment 147, which has the effect of increasing _{the C max of bupropion.}

Embodiment 149.
_{The effect of increasing the C max} of (S) -bupropion by at least 3 times is effective as _{compared with the C max} of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. 147. The method of embodiment 147 and 148.

Embodiment 150.
(S) -The method of embodiment 147, 148, or 149, which has the effect of increasing _{the AUC 0-12 of bupropion.}

Embodiment 151.
_{AUC 0-12 of} (S) _-bupropion is at least 3 times higher than AUC 0-12 of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. 147. The method of embodiment 147, 148, 149, or 150, which has the effect of increasing.

Embodiment 152.
147. The method of embodiment 147, 148, 149, 150 or 151, wherein the dosage form is administered at least once daily for at least consecutive 8 days.

Embodiment 153.
The oral dosage form is administered once daily for 1 to 3 consecutive days, followed by daily administration of the dosage form once or twice daily for a total of at least 8 consecutive days. The method of embodiment 152, wherein the dosage form is administered twice, at least for the next consecutive 4-7 days.

Embodiment 154.
147. The method of embodiment 147, 148, 149, 150, 151, 152, or 153, wherein the dosage form is well tolerated.

Embodiment 155.
Oral dosage forms containing at least about 90 mg of at least 95% isomerically pure (S) -bupropion-containing dosage forms orally to humans in need of treatment with (S) -bupropion and dextromethorphan. comprising administering, (S) - a method of increasing the plasma concentrations of bupropion, in the human (S) - _{C max} of at least 90 ng / mL next bupropion, (S) - the _{C max} of bupropion, When a dosage form containing the same amount of (R) -bupropion was administered to the human, it had the effect of increasing at least 3-fold compared to _{the C max of (R) -bupropion, and the human had dextromethorphan.} Not administered, method.

Embodiment 156.
The method of embodiment 155, wherein the oral dosage form is administered for at least 8 consecutive days.

Embodiment 157.
The oral dosage form is administered once daily for 1 to 3 consecutive days, followed by daily administration of the dosage form once or twice daily for a total of at least 8 consecutive days. 156. The method of embodiment 156, wherein the dosage form is administered twice, at least for the next consecutive 4-7 days.

Embodiment 158.
155, 156, or 157. The method of embodiment 155, 156, or 157, wherein the dosage form contains from about 100 mg to about 110 mg of (S) -bupropion.

Embodiment 159.
155. The method of embodiment 155, 156, 157, or 158, _{wherein the C max} of (S) -bupropion in the human is at least about 110 ng / mL.

Embodiment 160.
An oral dosage form containing at least about 90 mg of at least 95% isomerically pure (S) -bupropion is orally administered to humans in need of treatment with (R, R) -hydroxybupropion and dextromethorphan. said method _{comprising, (R, R) - C} max of at least about 90 ng / mL next hydroxy _{bupropion, (R, R) - C} max of hydroxy bupropion, the same amount of (R) - a dosage form comprising bupropion _{It has an effect of increasing at least 3-fold compared to the C max} of (R, R) -hydroxybupropion when administered to the human, and the human is not administered dextromethorphan, (R, R) -hydroxybupropion. How to increase the plasma concentration of.

Embodiment 161.
The method of embodiment 160, wherein the oral dosage form is administered for at least 8 consecutive days.

Embodiment 162.
The oral dosage form is administered once daily for 1 to 3 consecutive days, followed by daily administration of the dosage form once or twice daily for a total of at least 8 consecutive days. 161 according to embodiment 161 in which the dosage form is administered twice, at least for the next consecutive 4-7 days.

Embodiment 163.
16. The method of embodiment 160, 161 or 162, wherein the dosage form contains from about 100 mg to about 110 mg of (S) -bupropion.

Embodiment 164.
Enantiomeric excess capable of increasing dextromethorphan plasma concentration in humans compared to a reference oral dosage form containing the same amount of (S) -bupropion and the same amount of dextromethorphan. (R) -Oral dosage form containing bupropion and dextromethorphan.

Embodiment 165.
(R) -Oral dosage form containing bupropion and dextromethorphan, when orally administered to a human daily for at least 8 consecutive days, the plasma concentration of dextromethorphan in the human on day 1 or 8. The reference oral dosage form can be increased to a much greater extent than in the reference oral dosage form, the reference oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion.

Embodiment 166.
An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to a human daily for at least 8 consecutive days, results in an average C _max of day 1 dextromethorphan in the human being at least 150%. Increased, the reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion.

Embodiment 167.
An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in an average C _max of dextromethorphan on day 8 in the human being at least 25%. Increased, the reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion.

Embodiment 168.
When an oral dosage form containing (R) -bupropion and dextromethorphan is orally administered to a human daily for at least 8 consecutive days, the average C _max of dextromethorphan on day 8 in the human is referred to. An oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as lasemi-form bupropion, increased at least 20-fold compared to day 1 in the form.

Embodiment 169.
An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in an average C _max of day 1 dextromethorphan in the human being at least 60%. Increased, the reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion.

Embodiment 170.
An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in an average C _max of dextromethorphan on day 8 in the human being at least 20%. Increased, the reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion.

Embodiment 171.
To a much greater extent than when the oral reference dosage form was administered when orally administered to humans daily for at least 8 consecutive days, including oral administration of the dosage form containing (R) -bupropion and dextromethorphan. A method of increasing the plasma concentration of dextromethorphan on day 1 or 8, wherein the reference dosage form contains the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion.

Embodiment 172.
The dosage form or method according to embodiment 164, 165, 166, 167, 168, 168, 170, or 171 in which the (R) -bupropion in the dosage form is at least 95% enantiomerically pure. ..

Embodiment 173.
The dosage form or dosage form according to embodiment 164, 165, 166, 167, 168, 168, 170, or 171 in which the (S) -bupropion in the reference dosage form is at least 95% enantiomerically pure. Method.

Embodiment 174.
164, 165, 166, 167, 168, 168, 170, or 171. The dosage form or method according to embodiment 164, 165, 166, 167, 168, 168, 170, or 171.

Embodiment 175.
174. The dosage form or method of embodiment 174, wherein the dosage form contains from about 100 mg to about 110 mg of (R) -bupropion.

Embodiment 176.
164, 165, 166, 167, 168, 168, 170, or 171. The dosage form or method, wherein the dosage form contains from about 10 mg to about 50 mg of dextromethorphan.

Embodiment 177.
176. The dosage form or method of embodiment 176, wherein the dosage form contains from about 40 mg to about 50 mg of dextromethorphan.

Embodiment 178.
164, 165, 166, 167, 168, 168, 170, 171, 172, 173, 174, 175, 176, or 177, wherein the dosage form is orally administered once daily.

Embodiment 179.
164, 165, 166, 167, 168, 168, 170, 171, 172, 173, 174, 175, 176, or 177, wherein the dosage form is orally administered twice daily.

Embodiment 180.
The dosage form or method according to embodiment 178 or 179, wherein the dosage form is orally administered for at least consecutive 8 days.

Embodiment 181.
The dosage form or method according to embodiment 180, wherein the dosage form contains from about 100 mg to about 110 mg (R) -bupropion and from about 40 mg to about 50 mg dextromethorphan.

Embodiment 182.
The dosage form or method according to embodiment 180 or 181, _{wherein the average C max} of dextromethorphan is at least 80 ng / mL in the human on day 8 when the oral dosage form is orally administered daily for 8 consecutive days.

Embodiment 183.
The dosage form is syrup, tablet, capsule, spray. Or the dosage form or method according to embodiment 180, 181 or 182, which is in the form of a troche.

Embodiment 184.
A method for treating a neuropsychiatric disorder, comprising administering to a person in need of treatment the dosage form according to any of the above embodiments.

Embodiment 185.
A method of treating a cold or cough, comprising administering to a person in need of treatment the dosage form according to any of the above embodiments.

Embodiment 186.
A method of relieving pain, comprising administering to a person in need of relief the dosage form according to any of the above embodiments.

Embodiment 187.
A method of treating an addiction, comprising administering to a person in need of treatment the dosage form according to any of the above embodiments.

Embodiment 188.
Dosage forms containing at least 95% mirror imageically pure (S) -bupropion may be orally administered once or twice daily to humans who are ready to be treated with (S) -bupropion. A method of treating a human, including, wherein the amount of (S) -bupropion administered is selected from about 20% to about 70% of the amount of racemic bupropion administered to treat the same condition in the same human. How to be done.

Embodiment 189.
Therapeutically, including oral administration of at least 95% mirror image isomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. A method of providing an effective plasma concentration of (R, R) -hydroxybupropion, wherein (R, R) -hydroxybupropion is present in the human plasma with (R, R) -hydroxybupropion and (S). _{, S) -A method in which the C max} of (R, R) -hydroxybupropion in the human is at least 500 ng / mL, which is at least 97% of the total amount of -hydroxybupropion.

Embodiment 190.
A method of treating a human, comprising orally administering a dosage form containing at least 95% enantiomerically pure (S) -bupropion to a person in need of treatment with (S) -bupropion. The method, wherein the (S) -bupropion is the only active agent used to treat the human.

Embodiment 191.
Dosage forms containing at least 95% enantiomerically pure (S) -bupropion from about 50 mg to about 100 mg given orally once or twice daily to humans requiring treatment with (S) -bupropion. Methods of treating humans, including doing.

Embodiment 192.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of (S) -bupropion is at least about 60 ng / mL.

Embodiment 193.
Includes oral administration of a dosage form containing at least 95% mirror isomer pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, (R, R) -hydroxybupropion is at least 97% of the total amount of (R, R) -hydroxybupropion and (S, S) -hydroxybupropion present in the human plasma. Is the way.

Embodiment 194.
Therapeutically, including oral administration of at least 95% mirror image isomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. A method of providing an effective plasma concentration of (R, R) -hydroxybupropion, wherein (R, R) -hydroxybupropion is present in the human plasma with (R, R) -hydroxybupropion and (S). , S) -A method that is at least 97% of the total amount of hydroxybupropion.

Embodiment 195.
Therapeutically, including oral administration of at least 95% mirror image isomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. A method of providing an effective plasma concentration of (R, R) -hydroxybupropion, wherein the C _max of (R, R) -hydroxybupropion in the human is at least about 500 ng / mL.

Embodiment 196.
Described in any of the above embodiments, such as embodiments 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 193, 194, or 195, wherein dextromethorphan is not administered to the human. Method.

Embodiment 197.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of (S) -bupropion is at least about 70 ng / mL.

Embodiment 198.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of (S) -bupropion is at least about 600 ng · h / mL.

Embodiment 199.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of (R, R) -hydroxybupropion is at least about 800 ng / mL.

Embodiment 200.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of (R, R) -hydroxybupropion is at least about 8,000 ng · h / mL.

Embodiment 201.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of erythrohydroxybupropion is at least about 90 ng / mL.

Embodiment 202.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of erythrohydroxybupropion is at least about 1,000 ng · h / mL.

Embodiment 203.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of treohydroxybupropion is at least about 450 ng / mL.

Embodiment 204.
Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of treohydroxybupropion is at least about 5,000 ng · h / mL.

Embodiment 205.
Dosage form containing at least 95% enantiomerically pure (S) -bupropion.

Embodiment 206.
The dosage form of embodiment 205, comprising from about 100 mg to about 200 mg of (S) -bupropion.

Embodiment 207.
The dosage form according to any of the above embodiments, which comprises less than 0.1% of the other active agent.

Embodiment 208.
The dosage form according to any of the above embodiments, further comprising dextromethorphan.

Embodiment 209.
The dosage form according to embodiment 208, which comprises from about 10 mg to about 50 mg of dextromethorphan.

Embodiment 210.
The plasma concentration of (S) -bupropion or a metabolite thereof comprising administering the dosage form according to embodiment 205, 206, 207, 208, or 209 to a human in need of treatment with bupropion or a metabolite thereof. How to raise.

Embodiment 211.
(S) -The method according to any of the above embodiments, which has the effect of increasing _{the C max of bupropion.}

Embodiment 212.
_{The effect of increasing the C max} of (S) -bupropion by at least 3 times is effective as _{compared with the C max} of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. A method according to any of the above embodiments.

Embodiment 213.
(S) -The method according to any of the above embodiments, which has the effect of increasing _{the AUC 0-12 of bupropion.}

Embodiment 214.
_{AUC 0-12 of} (S) _-bupropion is at least 3 times higher than AUC 0-12 of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. The method according to any of the above embodiments, which has the effect of increasing.

Embodiment 215.
(R, R)-The method according to any of the above embodiments, which has the effect of increasing _{the C max of hydroxybupropion.}

Embodiment 216.
At least _{the C max} of (R, R) -hydroxybupropion was compared to _{the C max} of (R, R) -hydroxybupropion when the dosage form containing the same amount of (R) -bupropion was administered to the human. The method according to any of the above embodiments, which has the effect of increasing by a factor of three.

Embodiment 217.
The method according to any of the above embodiments, which has the effect of increasing _{the AUC 0-12} of (R, R) -hydroxybupropion.

Embodiment 218.
The same amount of (R) - a dosage form comprising bupropion when administered to the human (R, R) - compared to the _{AUC 0-12} of hydroxy bupropion, (R, R) - AUC 0 hydroxy bupropion 13. The method of embodiment 13, which has the effect of increasing _{-12 by at least 3-fold.}

Embodiment 219.
The method of any of the above embodiments, wherein the dosage form is administered at least once daily for at least consecutive 8 days.

Embodiment 220.
A method of treating a neurological condition, comprising administering to a human in need of treatment the dosage form according to any of the above embodiments.

Embodiment 221.
16. The method of embodiment 16, wherein the nerve condition is depression.

Embodiment 222.
A method of increasing plasma concentration of dextromethorphan, comprising administering a combination of (R) -bupropion and dextromethorphan to a person in need of treatment with dextromethorphan, said (R) -bupropion. Is at least 95% enantiomerically pure, the method.

Embodiment 223.
18. The method of embodiment 18, wherein _{the C max of} dextromethorphan is increased by 20% as compared to administration of the same amount of (S) -bupropion and the same amount of dextromethorphan.

Embodiment 224.
A method for delivering (S) -bupropion to human plasma, comprising orally administering to a human a dosage form containing at least 95% enantiomerically pure (S) -bupropion.

Embodiment 225.
Delivering both (R) -bupropion and (S) -bupropion to human plasma, including oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion to humans. A method in which the C _max of (R) -bupropion is within 20% _{of the C max} of (R) -bupropion when the same amount of racemic bupropion is administered to the human.

Embodiment 226.
A method of delivering bupropion to human plasma, comprising orally administering to human a dosage form containing at least 95% mirror image isomer pure (S) -bupropion, the AUC of (R) -bupropion. _0-12 is within 20% _{of AUC 0-12} of (R) -bupropion when the same amount of racemic bupropion is administered to the human.

Embodiment 227.
A method of delivering bupropion to human plasma, comprising orally administering to human a dosage form containing at least 95% enantiomerically pure (S) -bupropion, wherein (R, R) -hydroxy _{C max} of bupropion, when the same amount of racemic bupropion was administered to the human (R, R) - within 20% of the _{C max} of hydroxy bupropion method.

Embodiment 228.
224. The method of embodiment 224, 225, 226, or 227, wherein the (S) -bupropion is administered for at least consecutive 8 days.

Embodiment 229.
(S) -The method of embodiment 228, wherein bupropion is administered for at least 14 consecutive days.

Embodiment 230.
224. The method of embodiment 224, 225, 226, 227, 228, or 229, wherein the dosage form contains from about 50 mg to about 150 mg of (S) -bupropion.

Embodiment 231.
224. The method of embodiment 224, 225, 226, 227, 228, or 229, wherein the dosage form contains from about 40 mg to about 90 mg of (S) -bupropion.

Embodiment 232.
The method according to any of the above embodiments, wherein _{the combined C max} of (S) -bupropion and (R) -bupropion on day 8 is at least about 100 ng / mL as a result of administration of the dosage form.

Embodiment 233.
_{Described in any of the above embodiments, wherein the combined AUC 0-12} of (S) -bupropion and (R) -bupropion on day 8 as a result of administration of the dosage form is at least about 800 ng · h / mL. the method of.

Embodiment 234.
_{As a result of administration of the dosage form, the combined C max} of (S, S) -hydroxybupropion and (R, R) -hydroxybupropion on the 8th day is at least about 1,000 ng / mL, any of the above. The method according to the embodiment.

Embodiment 235.
_{As a result of administration of the dosage form, the combined AUC 0-12} of (S, S) -hydroxybupropion and (R, R) -hydroxybupropion on the 8th day is at least about 10,000 ng · h / mL. The method according to any one of the embodiments.

Embodiment 236.
The method according to any of the above embodiments, wherein _{the C max} of erythrohydroxybupropion on day 8 is at least about 100 ng / mL as a result of administration of the dosage form.

Embodiment 237.
The method according to any of the above embodiments, wherein _{the AUC 0-12} of erythrohydroxybupropion on day 8 results in at least about 1,500 ng · h / mL as a result of administration of the dosage form.

Embodiment 238.
The method according to any of the above embodiments, wherein _{the C max} of the treohydroxypropion on day 8 is at least about 600 ng / mL as a result of administration of the dosage form.

Embodiment 239.
The method according to any of the above embodiments, wherein _{the AUC 0-12} of the treohydroxybupropion on day 8 results in at least about 5,000 ng · h / mL as a result of administration of the dosage form.

Unless otherwise stated, the numbers representing properties such as the amount, amount, AUC value of the components used herein and in the claims are, in all cases, the exact values shown and " It should be understood as indicating both the values modified by the term "about". Therefore, unless otherwise indicated, the numerical parameters described herein and in the appended claims are approximations that may vary depending on the desired properties to be obtained. At the very least, it does not attempt to limit its application as an equivalent to the claims, and each numerical parameter is at least interpreted by applying conventional rounding means in the light of the number of significant figures reported. Should be.

The terms "a", "an", "the", and similar references used in the context of describing the invention (especially in the context of the following claims) are apparent unless otherwise stated or by context. Should be construed as covering both the singular and the plural, as long as they are not inconsistent with. The use of all examples, or exemplary languages (eg, "like") provided herein is intended to better clarify the invention and is claimed. There are no restrictions on. The statements herein should not be construed as indicating non-claims essential to the practice of the present invention.

The grouping of alternative elements or embodiments disclosed herein should not be construed as limiting. The components of each group may be referenced and claimed individually or in any combination with other components of the group or other elements found herein. For convenience and patentability reasons, it is expected that one or more components of a group will be included in or removed from the group. If such inclusion or deletion occurs, the specification is deemed to include the modified group and satisfies all statements of the Markush group used in the appended claims.

This specification describes some embodiments of the present invention, including the best embodiments known to the inventor for carrying out the present invention. Of course, variations of these described embodiments will be apparent to those skilled in the art by reading the above description. The inventor expects one of ordinary skill in the art to properly use such modifications, and the inventor intends to implement the invention in ways other than those specifically described herein. Therefore, the scope of claims includes all changes in subject matter and equivalents described in the scope of claims, as permitted by applicable law. Moreover, all possible combinations of the above-mentioned elements are conceivable, unless otherwise stated herein or as clearly contradictory to the context.

Finally, it should be understood that the embodiments disclosed herein exemplify the principles of the claims. Other changes that may be adopted are within the scope of the claims. Therefore, the alternative configuration of the present invention can be used as an embodiment, but not as limited, as taught herein. Therefore, the scope of claims is not exactly limited to embodiments as shown and described.

Claims (239)

Plasma bupropion or metabolites thereof, comprising orally administering to humans at least once daily a dosage form containing at least 95% enantiomerically pure about 50 mg to about 100 mg (S) -bupropion. Method of delivery. To select human patients who require a pharmacokinetic profile obtained by orally administering a reference dosage form containing a first amount of racemic bupropion at a first frequency of administration.
A dosage form containing a second amount of (S) -bupropion that is at least 95% enantiomerically pure is orally administered at the first dose frequency and the reference dosage form is administered at the first dose frequency. To achieve the same pharmacokinetic profile achieved by administration,
Including
The first administration frequency is once a day or twice a day.
The second amount is about 40% to about 60% of the first amount.
A method of delivering bupropion to human plasma. To select human patients with a condition that can be treated by oral administration of a reference dosage form containing a first amount of racemic bupropion at the first frequency of administration.
A dosage form containing a second amount of (S) -bupropion that is at least 95% enantiomerically pure is orally administered at the first dose frequency and the reference dosage form is administered at the first dose frequency. To achieve the same therapeutic effect as achieved by administration,
Including
The first administration frequency is once a day or twice a day.
The second amount is about 40% to about 60% of the first amount.
A method of treating a condition that can be treated with racemic bupropion. The method of claim 1, wherein the human is in need of treatment with (S) -bupropion. (S) -The method of claim 1, 2, 3, or 4, wherein _{the C max of bupropion is at least about 60 ng / mL. The effect of increasing the C max} of (S) -bupropion by at least 5 times as _{compared with the C max} of (R) -bupropion when the same amount of (R) -bupropion is administered to humans, claim 1, 2, 3, 4, or 5. The method of claim 1, 2, 3, 4, 5, or 6, _{wherein the C max} of (R, R) -hydroxybupropion in humans is at least about 500 ng / mL. _{The effect of increasing the C min} of (R, R) -hydroxybupropion by at least 3 times as _{compared with the C min} of (R, R) -hydroxybupropion when the same amount of (R) -bupropion was administered to the human. The method according to claim 1, 2, 3, 4, 5, 6, or 7. The method according to claim 1, 2, 3, 4, 5, 6, 7, or 8, wherein the dosage form is administered once a day. The method of claim 1, 2, 3, 4, 5, 6, 7, or 8, wherein the dosage form is administered twice daily. Claims 1, 2, 2. The (R, R) -hydroxybupropion is at least 97% of the total amount of (R, R) -hydroxybupropion and (S, S) -hydroxybupropion present in the human plasma. 3, 4, 5, 6, 7, 8, 9, or 10. The method of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11, which has the effect of providing a therapeutically effective plasma concentration of (R, R) -hydroxybupropion. .. (S) -The method of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, which has the effect of providing a therapeutically effective plasma concentration of bupropion. The method of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, wherein the human needs treatment with (R, R) -hydroxybupropion. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 such that _{the C max} of (R, R) -hydroxybupropion in the human is at least about 500 ng / mL. , Or the method according to 14. The method of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, wherein the dosage form is administered for at least consecutive 8 days. 16. The method of claim 16, wherein the dosage form is administered for at least 14 consecutive days. 16. The method of claim 16, wherein the dosage form is administered for at least 21 consecutive days. Claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15, wherein the dosage form contains from about 60 mg to about 90 mg of (S) -bupropion. , 16, 17 or 18. The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 in which the dosage form is administered once, at least for the next consecutive 4-7 days. , 16, 17, 18, or 19. The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 in which the dosage form is administered once, at least for the next seven consecutive days. , 17, 18, 19, or 20. Claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14, wherein the dosage form contains from about 70 mg to about 80 mg of the (S) -bupropion. 15, 16, 17, 18, 19, 20, or 21. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, _{14, etc., wherein the C max} of (S) -bupropion in the human is at least about 70 ng / mL. 15, 16, 17, 18, 19, 20, 21, or 22. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc., _{wherein the AUC 0-12} of (S) -bupropion in the human is at least about 400 ng · hr / mL. 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23. _{24. The method of claim 24, wherein the AUC 0-12} of (S) -bupropion in humans is at least about 500 ng · hr / mL to about 900 ng · hr / mL. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 that the dosage form sustainedly releases the (S) -bupropion. , 18, 19, 20, 21, 22, 23, 24, or 25. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, which further contain dextromethorphan. 19, 20, 21, 22, 23, 24, 25, or 26. Claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14, wherein the dosage form contains from about 70 mg to about 80 mg of the (S) -bupropion. 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 such that _{the C max} of (R, R) -hydroxybupropion in the human is at least about 600 ng / mL. , 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28. Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 such that _{the AUC 0-12} of (R, R) -hydroxybupropion in humans is at least about 7,000 ng · hr / mL. , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29. _{30. The method of claim 30, wherein the AUC 0-12} of (R, R) -hydroxybupropion in humans is at least about 8000 ng · hr / mL. For humans requiring treatment with dextromethorphan and at least about 90 mg of at least 95% microscopically pure (S) -bupropion at least once daily with both (S) -bupropion and dextromethorphan. Including co-administration _{of (R) -bupropion in the human, the C max} of (S) -bupropion was at least about 90 ng / mL, and the same amount of (R) -bupropion was administered to the human. compared to C _max, (S) - it has the effect of increasing at least 3-fold the C _max of bupropion, (S) - method of increasing the plasma concentrations of bupropion and dextromethorphan. 32. The method of claim 32, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days. 32. The method of claim 32, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 14 consecutive days. 32. The method of claim 32, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form. The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 33, 34, or 35, wherein the dosage form is administered once, at least for the next consecutive 4-7 days. The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 33. The method of claim 33, 34, or 35, wherein the dosage form is administered once, at least for the next seven consecutive days. The method of claim 32, 33, 34, 35, 36, or 37, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion. The method of claim 32, 33, 34, 35, 36, 37 or 38, _{wherein the C max} of (S) -bupropion in humans is at least about 110 ng / mL. The method of claim 32, 33, 34, 35, 36, 37, 38 or 39, _{wherein the AUC 0-12} of (S) -bupropion in humans is at least about 800 ng · hr / mL. The method according to claim 32, 33, 34, 35, 36, 37, 38, 39 or 40, wherein the (S) -bupropion is administered in a dosage form in which the (S) -bupropion is sustained-release. Needs treatment with dextromethorphan and at least about 90 mg of at least 95% microscopically pure (S) -bupropion at least once daily with both (R, R) -hydroxybupropion and dextromethorphan. _{When the C max} of (R, R) -hydroxybupropion in the human is at least about 700 ng / mL and the same amount of (R) -bupropion is administered to the human, including oral co-administration to the human. _{The effect of increasing the C max} of (R, R) -hydroxybupropion by at least 3-fold compared to the C _{max of} (R, R) -hydroxybupropion, of (R, R) -hydroxybupropion and dextromethorphan A method of increasing plasma concentration. 42. The method of claim 42, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days. 42. The method of claim 42, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least two consecutive 21 days. 42. The method of claim 42, 43, or 44, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form. The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 42. The method of claim 42, 43, 44, or 45, wherein the dosage form is administered once, at least for the next consecutive 4-7 days. The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. 42. The method of claim 42, 43, 44, 45, or 46, wherein the dosage form is administered once, at least for the next seven consecutive days. The method of claim 42, 43, 44, 45, 46, or 47, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion. 42, 43, 44, 45, 46, 47, or 48, _{wherein the C max} of (R, R) -hydroxybupropion in humans is at least about 900 ng / mL. 42, 43, 44, 45, 46, 47, 48, or 49, _{wherein the AUC 0-12} of (R, R) -hydroxybupropion in humans is at least about 10,000 ng · hr / mL. Method. The method according to claim 42, 43, 44, 45, 46, 47, 48, 49, or 50, wherein the (S) -bupropion is administered in a dosage form that sustainedly releases the (S) -bupropion. At least once daily, at least about 90 mg of at least 95% microscopically pure (S) -bupropion comprises orally administered to a person in need of treatment with (S) -bupropion, said human. _{The C min} of (S) -bupropion in (S) was at least about 20 ng / mL, as compared with _{the C min} of (R) -bupropion when a dosage form containing the same amount of (R) -bupropion was administered to the human. , (S) -A method of increasing the plasma concentration of bupropion, which has the effect of increasing _{the C min of (S) -bupropion by at least 3-fold.} 52. The method of claim 52, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days. 52. The method of claim 52, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 14 consecutive days. The method of claim 52, 53, or 54, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form. The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. The method of claim 52, 53, 54, or 55, wherein the dosage form is administered once, at least for the next consecutive 4-7 days. The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. The method of claim 52, 53, 54, 55, or 56, wherein the dosage form is administered once, at least for the next seven consecutive days. The method of claim 52, 53, 54, 55, 56, or 57, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion. The method of claim 52, 53, 54, 55, 56, 57, or 58, _{wherein the C max} of (S) -bupropion in humans is at least about 110 ng / mL. 52, 53, 54, 55, 56, 57, 58, or 59, _{wherein the AUC 0-12} of (S) -bupropion in humans is at least about 800 ng · hr / mL. (S) -The method of claim 52, 53, 54, 55, 56, 57, 58, 59 or 60, wherein the (S) -bupropion is administered in a dosage form that sustainedly releases (S) -bupropion. Includes oral administration of at least about 90 mg of at least 95% mirror isomerically pure (S) -bupropion at least once daily to humans in need of treatment with (R, R) -hydroxybupropion. , in the human (R, R) - _{C min} of at least about 700 ng / mL next hydroxy bupropion, the same amount of (R) - when administered bupropion to said human (R, R) - hydroxy bupropion _{C min} A method of increasing the plasma concentration of (R, R) -hydroxybupropion, which has the effect of increasing _{the C min} of (R, R) -hydroxybupropion by at least 3-fold as compared to. 62. The method of claim 62, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least 8 consecutive days. 62. The method of claim 62, wherein the dextromethorphan and the (S) -bupropion are co-administered for at least two consecutive 21 days. The method of claim 62, 63, or 64, wherein the dextromethorphan and the (S) -bupropion are co-administered in a single dosage form. The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. The method of claim 62, 63, 64, or 65, wherein the dosage form is administered once, at least for the next consecutive 4-7 days. The dosage form is administered once daily for 1 to 7 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. The method of claim 62, 63, 64, 65 or 66, wherein the dosage form is administered once, at least for the next seven consecutive days. The method of claim 62, 63, 64, 65, 66 or 67, wherein the (S) -bupropion is administered in a dosage form containing from about 100 mg to about 110 mg of the (S) -bupropion. 62, 63, 64, 65, 66, 67, or 68, _{wherein the C max} of (R, R) -hydroxybupropion in humans is at least about 900 ng / mL. 62, 63, 64, 65, 66, 67, 68, or 69, _{wherein the AUC 0-12} of (R, R) -hydroxybupropion in humans is at least about 10,000 ng · hr / mL. Method. The method according to claim 62, 63, 64, 65, 66, 67, 68, 69, or 70, wherein the (S) -bupropion is administered in a dosage form that sustainedly releases the (S) -bupropion. A method of treating central nervous system (CNS) disorders in humans, in which a therapeutically effective amount of at least about 95% enantiomerically pure (S) -bupropion-containing dosage form and dextromethorphan is administered to humans. Methods, including treating CNS disorders. 72. The method of claim 72, wherein the CNS disorder includes depression. 72. The method of claim 72, wherein the CNS disorder comprises treatment-resistant depression. 72. The method of claim 72, wherein the CNS disorder includes an addictive disorder. 72. The method of claim 72, wherein the CNS disorder comprises nicotine addiction. 72. The method of claim 72, wherein the CNS disorder comprises alcoholism. 72. The method of claim 72, wherein the CNS disorder includes Alzheimer's disease. The method of claim 72, 73, 74, 75, 76, 77, or 78, wherein the dosage form is a tablet, capsule, or syrup. The method of claim 72, 73, 74, 75, 76, 77, 78, or 79, wherein the dosage form is orally administered to the human. The method of claim 72, 73, 74, 75, 76, 77, 78, 79, or 80, wherein the dosage form is orally administered to the human daily. The method of claim 72, 73, 74, 75, 76, 77, 78, 79, 80, or 81, wherein the dosage form is orally administered to the human once daily. The method of claim 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, or 82, wherein the dosage form is orally administered to the human twice daily. The method of claim 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, or 83, wherein the dosage form is orally administered to the human under fasting conditions. The method of claim 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, or 84, wherein the dosage form is orally administered to the human daily for at least 8 consecutive days. Claim 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, or 85, wherein the dosage form contains from about 100 mg to about 200 mg of the (S) -bupropion. The method described in. Claims 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, wherein the dosage form contains from about 104 mg to about 106 mg of the (S) -bupropion. Alternatively, the method according to 86. Claims 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, wherein the dosage form contains from about 148 mg to about 152 mg of the (S) -bupropion. 86, or 87. Claims 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, wherein both the (S) -bupropion and the dextromethorphan are included in the dosage form. 85, 86, 87, or 88. Claims 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, wherein the dosage form contains from about 10 mg to about 50 mg of the dextromethorphan. 87, 88, or 89. Claims 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, wherein the dosage form contains from about 44 mg to about 46 mg of the dextromethorphan. 87, 88, 89, or 90. The dosage form is well tolerated, claim 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, or 91. Of dextromethorphan, including administration of a therapeutically effective amount of a dosage form and dextromethorphan containing at least about 95% enantiomerically pure (S) -bupropion to humans in need of treatment with bupropion. A method of increasing the plasma concentration of (S) -bupropion while increasing the plasma concentration. 39. The method of claim 93, which has the effect of increasing _{the C max} of (S) -bupropion as compared to administration of the same amount of racemic bupropion. (S) - the C _max of bupropion, the same amount of (R) - in the case of a dosage form comprising bupropion was administered to the human (R) - there are at least 3 times higher that the effect of the C _max of bupropion, wherein Item 93 or 94. The method of claim 93, 94, or 95, which has the effect of increasing _{the AUC 0-12} of (S) -bupropion as compared to administration of the same amount of racemic bupropion. (S) - the _{AUC 0-12} of bupropion, the same amount of (R) - when a dosage form comprising bupropion was administered to the human (R) - at least 3 times higher that the effect of bupropion _{AUC 0-12} The method of claim 96. The method of claim 95, 96, or 97, wherein the dosage form is administered at least once daily for at least consecutive 8 days. The dosage form is administered once daily for 1 to 3 consecutive days, followed by 2 daily doses such that the dosage form is administered once daily or twice daily for a total of at least 8 consecutive days. The method of claim 95, 96, 97, or 98, wherein the dosage form is administered once, at least for the next consecutive 4-7 days. The method of claim 95, 96, 97, 98, or 99, wherein the dosage form is well tolerated. A dosage form containing at least about 95% mirror image of isomerically pure (R) -bupropion and dextromethorphan, which can be administered orally to humans in equal amounts of (S) -bupropion and dextromethorphan. A dosage form capable of increasing the plasma concentration of dextromethorphan in said humans as compared to oral administration of a reference dosage form containing the same amount of dextromethorphan. 10. The dosage form of claim 101, comprising from about 100 mg to about 200 mg of (R) -bupropion. 10. The dosage form of claim 102, comprising from about 104 mg to about 106 mg of (R) -bupropion. The dosage form of claim 102, comprising from about 148 mg to about 152 mg of (R) -bupropion. The dosage form of claim 101, 102, 103, or 104, which comprises from about 10 mg to about 50 mg of dextromethorphan. The dosage form of claim 105, which comprises from about 44 mg to about 46 mg of dextromethorphan. 10. The dosage form of claim 101, comprising from about 100 mg to about 110 mg (R) -bupropion and from about 40 mg to about 50 mg dextromethorphan. The dosage form according to claim 101, 102, 103, 104, 105, 106, or 107, which is orally administered to the human daily. The dosage form according to claim 101, 102, 103, 104, 105, 106, 107, or 108, which is orally administered to the human once daily. The dosage form according to claim 101, 102, 103, 104, 105, 106, 107, or 108, which is orally administered to the human twice daily. The dosage form according to claim 109 or 110, which is orally administered to the human daily for at least 8 consecutive days. The dosage form according to claim 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, or 111, which is orally administered to the human under fasting conditions. The dosage form of claim 111, wherein on the 8th day of daily oral administration of the dosage form for 8 consecutive days, the C _max of dextromethorphan in the human is at least about 80 ng / mL. The dosage form of claim 113, which is in the form of a syrup, tablet, capsule, spray, or troche. The dosage form of claim 113 or 114, which is used to treat a neuropsychiatric disorder in said human in need of treatment. Claims 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, used to treat a cold or cough in said human in need of treatment. Alternatively, the dosage form according to 115. Claims 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, or 115, which are used to relieve pain in said humans in need of relief. Dosage form described in. Claims 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, or 115, used to treat addiction in humans in need of treatment. Dosage form described in. Claims 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, which are well tolerated when administered to said human. , Or the dosage form according to 118. Containing the administration of a dosage form to humans containing at least about 95% enantiomerically pure (R) -bupropion and dextromethorphan, with said dosage form being the same amount of (S) -bupropion and the same amount. A method for increasing the plasma concentration of dextromethorphan in humans, which can increase the plasma concentration of dextromethorphan in humans, as compared to a reference dosage form containing dextromethorphan. The method of claim 120, wherein the dosage form contains from about 100 mg to about 200 mg of (R) -bupropion. The method of claim 120, wherein the dosage form contains from about 100 mg to about 110 mg of (R) -bupropion. The method of claim 120, wherein the dosage form contains from about 148 mg to about 152 mg of (R) -bupropion. The method of claim 120, 121, 122, or 123, wherein the dosage form contains from about 10 mg to about 50 mg of dextromethorphan. The method of claim 124, wherein the dosage form contains from about 40 mg to about 50 mg of dextromethorphan. 12. The method of claim 125, wherein the dosage form contains from about 100 mg to about 110 mg (R) -bupropion and from about 40 mg to about 50 mg dextromethorphan. The method of claim 120, 121, 122, 123, 124, 125, or 126, wherein the dosage form is orally administered to the human under fasting conditions. The method of claim 120, 121, 122, 123, 124, 125, 126, or 127, wherein the dosage form is well tolerated. A method of treating central nervous system (CNS) disorders in humans, in which a dosage form containing at least about 95% enantiomerically pure (S) -bupropion of a therapeutically effective amount is administered to humans for CNS disorders. The method comprising treating the human being not administered dextromethorphan. 129. The method of claim 129, wherein the CNS disorder includes depression. 129 or 130. The method of claim 129 or 130, wherein the CNS disorder comprises treatment-resistant depression. The method of claim 129, 130, or 131, wherein the CNS disorder is an addictive disorder. The method of claim 132, wherein the CNS disorder is nicotine addiction. The method of claim 132, wherein the CNS disorder is alcoholism. The method of claim 132, wherein the CNS disorder is Alzheimer's disease. The method of claim 129, 130, 131, 132, 133, 134, or 135, wherein the dosage form contains no active agent other than (S) -bupropion. The method of claim 129, 130, 131, 132, 133, 134, or 135, wherein the dosage form contains less than 0.1% of the active agent in addition to (S) -bupropion. 129, 130, 131, 132, 133, 134, 135, 136, or 137, wherein the dosage form is in the form of tablets, capsules, or syrups. 129, 130, 131, 132, 133, 134, 135, 136, 137, or 138, wherein the dosage form is orally administered to the human daily. 139. The method of claim 139, wherein the dosage form is orally administered to the human once daily. 139. The method of claim 139, wherein the dosage form is orally administered to the human twice daily. The method of claim 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, or 141, wherein the dosage form is orally administered to the human under fasting conditions. 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, or 142, wherein the dosage form is orally administered to the human daily for at least 8 consecutive days. the method of. Claims 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, or 143. 14. The method of claim 144, wherein the dosage form contains from about 104 mg to about 106 mg of (S) -bupropion. 14. The method of claim 144, wherein the dosage form contains from about 148 mg to about 152 mg of (S) -bupropion. Plasma concentration of (S) -bupropion, comprising administering to a human in need of treatment with bupropion a dosage form containing at least about 95% enantiomerically pure (S) -bupropion of a therapeutically effective amount. A method in which the dosage form does not contain dextromethorphan. (S) -The method of claim 147, which has the effect of increasing _{the C max of bupropion. The effect of increasing the C max} of (S) -bupropion by at least 3 times is effective as _{compared with the C max} of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. 147. The method of claim 147 and 148. (S)-The method of claim 147, 148, or 149, which has the effect of increasing _{the AUC 0-12 of bupropion. AUC 0-12 of} (S) _-bupropion is at least three times higher than AUC 0-12 of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. 147. The method of claim 147, 148, 149, or 150, which has the effect of increasing. The method of claim 147, 148, 149, 150 or 151, wherein the dosage form is administered at least once daily for at least consecutive 8 days. The oral dosage form is administered once daily for 1 to 3 consecutive days, followed by daily administration of the dosage form once or twice daily for a total of at least 8 consecutive days. 15. The method of claim 152, wherein the dosage form is administered twice, at least for the next consecutive 4-7 days. 147. The method of claim 147, 148, 149, 150, 151, 152, or 153, wherein the dosage form is well tolerated. Oral dosage forms containing at least about 90 mg of at least 95% isomerically pure (S) -bupropion-containing dosage forms orally to humans requiring treatment with (S) -bupropion and dextromethorphan. comprising administering, (S) - a method of increasing the plasma concentrations of bupropion, in the human (S) - _{C max} of at least 90 ng / mL next bupropion, (S) - the _{C max} of bupropion, When a dosage form containing the same amount of (R) -bupropion was administered to the human, it had an effect of increasing at least 3-fold as compared with _{the C max of (R) -bupropion, and the human had dextromethorphan.} Not administered, method. The method of claim 155, wherein the oral dosage form is administered for at least 8 consecutive days. The oral dosage form is administered once daily for 1 to 3 consecutive days, followed by daily administration of the dosage form once or twice daily for a total of at least 8 consecutive days. 156. The method of claim 156, wherein the dosage form is administered twice, at least for the next consecutive 4-7 days. The method of claim 155, 156, or 157, wherein the dosage form contains from about 100 mg to about 110 mg of (S) -bupropion. 155. The method of claim 155, 156, 157, or 158, _{wherein the C max} of (S) -bupropion in humans is at least about 110 ng / mL. An oral dosage form containing at least about 90 mg of at least 95% isomerically pure (S) -bupropion is orally administered to humans in need of treatment with (R, R) -hydroxybupropion and dextromethorphan. said method _{comprising, (R, R) - C} max of at least about 90 ng / mL next hydroxy _{bupropion, (R, R) - C} max of hydroxy bupropion, the same amount of (R) - a dosage form comprising bupropion _{The effect is to increase at least 3-fold compared to the C max} of (R, R) -hydroxybupropion when administered to the human, and the human is not administered dextromethorphan, (R, R) -hydroxybupropion. How to increase the plasma concentration of. The method of claim 160, wherein the oral dosage form is administered for at least 8 consecutive days. The oral dosage form is administered once daily for 1 to 3 consecutive days, followed by daily administration of the dosage form once or twice daily for a total of at least 8 consecutive days. 161. The method of claim 161, wherein the dosage form is administered twice, at least for the next consecutive 4-7 days. The method of claim 160, 161 or 162, wherein the dosage form contains from about 100 mg to about 110 mg of (S) -bupropion. Enantiomeric excess capable of increasing dextromethorphan plasma concentration in humans compared to a reference oral dosage form containing the same amount of (S) -bupropion and the same amount of dextromethorphan. (R) -Oral dosage form containing bupropion and dextromethorphan. (R) -Oral dosage form containing bupropion and dextromethorphan, when orally administered to humans daily for at least 8 consecutive days, the plasma concentration of dextromethorphan in said human on day 1 or 8. The reference oral dosage form can be increased to a much greater extent than in the reference oral dosage form, wherein the reference oral dosage form contains the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion. An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in at least 150% _{of the average C max of dextromethorphan on day 1 in said humans.} Increased, said reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion. An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in at least 25% _{of the average C max of dextromethorphan on day 8 in said humans.} Increased, said reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion. (R) -Oral dosage form containing bupropion and dextromethorphan, when orally administered to humans daily for at least 8 consecutive days, the average C _max of dextromethorphan on day 8 in said humans, see above. The reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as lasemi-form bupropion, increased at least 20-fold compared to day 1 for the dosage form. An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in at least 60% _{of the average C max of dextromethorphan on day 1 in said humans.} Increased, said reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion. An oral dosage form containing (R) -bupropion and dextromethorphan that, when orally administered to humans daily for at least 8 consecutive days, results in at least 20% _{of the average C max of dextromethorphan on day 8 in said humans.} Increased, said reference oral dosage form is an oral dosage form containing the same amount of bupropion and the same amount of dextromethorphan as the racemic bupropion. To a much greater extent than when the oral reference dosage form was administered when orally administered to humans daily for at least 8 consecutive days, including oral administration of the dosage form containing (R) -bupropion and dextromethorphan. A method of increasing the plasma concentration of dextromethorphan on day 1 or 8, wherein the reference dosage form contains the same amount of bupropion and the same amount of dextromethorphan as (S) -bupropion. The dosage form or method according to claim 164, 165, 166, 167, 168, 168, 170, or 171 in which the (R) -bupropion in the dosage form is at least 95% enantiomerically pure. .. The dosage form or 171 according to claim 164, 165, 166, 167, 168, 168, 170, or 171 in which the (S) -bupropion in the reference dosage form is at least 95% enantiomerically pure. Method. The dosage form or method of claim 164, 165, 166, 167, 168, 168, 170, or 171, wherein the dosage form contains from about 100 mg to about 150 mg of (R) -bupropion. 174. The dosage form or method of claim 174, wherein the dosage form contains from about 100 mg to about 110 mg of (R) -bupropion. The dosage form or method according to claim 164, 165, 166, 167, 168, 168, 170, or 171. The dosage form contains about 10 mg to about 50 mg of dextromethorphan. 176. The dosage form or method of claim 176, wherein the dosage form contains from about 40 mg to about 50 mg of dextromethorphan. 164, 165, 166, 167, 168, 168, 170, 171, 172, 173, 174, 175, 176, or 177, wherein the dosage form is orally administered once daily. 164, 165, 166, 167, 168, 168, 170, 171, 172, 173, 174, 175, 176, or 177, wherein the dosage form is orally administered twice daily. The dosage form or method of claim 178 or 179, wherein the dosage form is orally administered for at least consecutive 8 days. The dosage form or method of claim 180, wherein the dosage form contains from about 100 mg to about 110 mg (R) -bupropion and from about 40 mg to about 50 mg dextromethorphan. The dosage form or method of claim 180 or 181, _{wherein the average C max} of dextromethorphan is at least 80 ng / mL in the human on day 8 when the oral dosage form is orally administered daily for 8 consecutive days. The dosage form is syrup, tablet, capsule, spray. Or the dosage form or method of claim 180, 181 or 182, which is in the form of a troche. A method of treating a neuropsychiatric disorder, comprising administering to a person in need of treatment the dosage form of any of the above claims. A method of treating a cold or cough, comprising administering to a person in need of treatment the dosage form according to any of the above claims. A method of relieving pain, comprising administering to a person in need of relief the dosage form according to any one of the above claims. A method of treating an addiction, comprising administering to a person in need of treatment the dosage form according to any one of the above claims. Dosage forms containing at least 95% mirror imageically pure (S) -bupropion may be orally administered once or twice daily to humans who are ready to be treated with (S) -bupropion. A method of treating a human, including, wherein the amount of (S) -bupropion administered is selected from about 20% to about 70% of the amount of racemic bupropion administered to treat the same condition in the same human. How to be done. Therapeutically, including oral administration of at least 95% mirror image isomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. A method of providing an effective plasma concentration of (R, R) -hydroxybupropion, wherein (R, R) -hydroxybupropion is present in the human plasma with (R, R) -hydroxybupropion and (S). _{, S) -A method in which the C max} of (R, R) -hydroxybupropion in a human is at least 500 ng / mL, which is at least 97% of the total amount of -hydroxybupropion. A method of treating a human, comprising orally administering a dosage form containing at least 95% enantiomerically pure (S) -bupropion to a person in need of treatment with (S) -bupropion. The method, wherein the (S) -bupropion is the only active agent used to treat the human. Dosage forms containing at least 95% enantiomerically pure (S) -bupropion from about 50 mg to about 100 mg given orally once or twice daily to humans requiring treatment with (S) -bupropion. Methods of treating humans, including doing. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of (S) -bupropion is at least about 60 ng / mL. Includes oral administration of a dosage form containing at least 95% mirror image isomer pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. In a method of treating humans, (R, R) -hydroxybupropion is at least 97% of the total amount of (R, R) -hydroxybupropion and (S, S) -hydroxybupropion present in the human plasma. Is the way. Therapeutically, including oral administration of at least 95% mirror image isomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. A method of providing an effective plasma concentration of (R, R) -hydroxybupropion, wherein (R, R) -hydroxybupropion is present in the human plasma with (R, R) -hydroxybupropion and (S). , S) -A method that is at least 97% of the total amount of hydroxybupropion. Therapeutically, including oral administration of at least 95% mirror image isomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (R, R) -hydroxybupropion. A method of providing an effective plasma concentration of (R, R) -hydroxybupropion, wherein the C _max of (R, R) -hydroxybupropion in the human is at least about 500 ng / mL. 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 193, 194, or 195, wherein dextromethorphan is not administered to the human. Method. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of (S) -bupropion is at least about 70 ng / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of (S) -bupropion is at least about 600 ng · h / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of (R, R) -hydroxybupropion is at least about 800 ng / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of (R, R) -hydroxybupropion is at least about 8,000 ng · h / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of erythrohydroxybupropion is at least about 90 ng / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of erythrohydroxybupropion is at least about 1,000 ng · h / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the C _max of treohydroxybupropion is at least about 450 ng / mL. Includes oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion once or twice daily to humans in need of treatment with (S) -bupropion. A method of treating humans, wherein the AUC _0-12 of treohydroxybupropion is at least about 5,000 ng · h / mL. Dosage form containing at least 95% enantiomerically pure (S) -bupropion. The dosage form of claim 205, comprising from about 100 mg to about 200 mg of (S) -bupropion. The dosage form of any of the above claims, comprising less than 0.1% of the other active agent. The dosage form of any of the above, further comprising dextromethorphan. The dosage form of claim 208, comprising from about 10 mg to about 50 mg dextromethorphan. Plasma concentration of (S) -bupropion or a metabolite thereof comprising administering the dosage form of claim 205, 206, 207, 208, or 209 to a human in need of treatment with bupropion or a metabolite thereof. How to raise. (S) -The method of any of the above claims, which has the effect of increasing _{the C max of bupropion. The effect of increasing the C max} of (S) -bupropion by at least 3 times is effective as _{compared with the C max} of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. A method according to any of the above claims. (S) -The method of any of the above claims, which has the effect of increasing _{the AUC 0-12 of bupropion. AUC 0-12 of} (S) _-bupropion is at least three times higher than AUC 0-12 of (R) -bupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. The method according to any of the above claims, which has the effect of increasing. (R, R)-The method of any of the above claims, which has the effect of increasing _{the C max of hydroxybupropion. The C max of} (R, R) -hydroxybupropion is at least _{C max} compared to the C max of (R, R) -hydroxybupropion when the dosage form containing the same amount of (R) -bupropion is administered to the human. The method according to any of the above claims, which has the effect of increasing by a factor of three. (R, R) _-The method of any of the above claims, which has the effect of increasing the AUC 0-12 of hydroxybupropion. The same amount of (R) - when a dosage form comprising bupropion administered to said human (R, R) - compared to the _{AUC 0-12} of hydroxy bupropion, (R, R) - AUC 0 hydroxy bupropion 13. The method of claim 13, which has the effect of increasing _{-12 by at least 3-fold.} The method of any of the above, wherein the dosage form is administered at least once daily for at least 8 consecutive days. A method of treating a neurological condition, comprising administering to a person in need of treatment the dosage form according to any of the above claims. 16. The method of claim 16, wherein the neural condition is depression. A method for increasing plasma concentration of dextromethorphan, which comprises administering a combination of (R) -bupropion and dextromethorphan to a person in need of treatment with dextromethorphan, wherein the (R) -bupropion. Is at least 95% enantiomerically pure, the method. The method of claim 18, wherein _{the C max of} dextromethorphan is increased by 20% as compared to administration of the same amount of (S) -bupropion and the same amount of dextromethorphan. A method for delivering (S) -bupropion to human plasma, comprising orally administering to a human a dosage form containing at least 95% enantiomerically pure (S) -bupropion. Delivering both (R) -bupropion and (S) -bupropion to human plasma, including oral administration of a dosage form containing at least 95% enantiomerically pure (S) -bupropion to humans. A method in which the C _max of (R) -bupropion is within 20% _{of the C max} of (R) -bupropion when the same amount of racemic bupropion is administered to said human. A method of delivering bupropion to human plasma, comprising orally administering to human a dosage form containing at least 95% mirror image isomer pure (S) -bupropion, the AUC of (R) -bupropion. _0-12 is within 20% _{of AUC 0-12} of (R) -bupropion when the same amount of racemic bupropion is administered to said human. A method of delivering bupropion to human plasma, comprising orally administering to human a dosage form containing at least 95% enantiomerically pure (S) -bupropion, wherein (R, R) -hydroxy _{C max} of bupropion, when the same dose of racemic bupropion in the human (R, R) - within 20% of the _{C max} of hydroxy bupropion method. The method of claim 224, 225, 226, or 227, wherein the (S) -bupropion is administered for at least consecutive 8 days. 228. The method of claim 228, wherein the (S) -bupropion is administered for at least 14 consecutive days. The method of claim 224, 225, 226, 227, 228, or 229, wherein the dosage form contains from about 50 mg to about 150 mg of (S) -bupropion. 224. The method of embodiment 224, 225, 226, 227, 228, or 229, wherein the dosage form contains from about 40 mg to about 90 mg of (S) -bupropion. The method according to any of the above embodiments, wherein the combined C _max of (S) -bupropion and (R) -bupropion on day 8 is at least about 100 ng / mL as a result of administration of the dosage form. _{Described in any of the above embodiments, wherein the combined AUC 0-12} of (S) -bupropion and (R) -bupropion on day 8 as a result of administration of the dosage form is at least about 800 ng · h / mL. the method of. _{As a result of administration of the above dosage form, the combined C max} of (S, S) -hydroxybupropion and (R, R) -hydroxybupropion on the 8th day is at least about 1,000 ng / mL, any of the above. The method according to the embodiment. _{As a result of administration of the above dosage form, the combined AUC 0-12} of (S, S) -hydroxybupropion and (R, R) -hydroxybupropion on the 8th day is at least about 10,000 ng · h / mL. The method according to any one of the embodiments. The method according to any of the above embodiments, wherein the C _max of erythrohydroxybupropion on day 8 is at least about 100 ng / mL as a result of administration of the dosage form. The method according to any of the above embodiments, wherein the AUC _0-12 of erythrohydroxybupropion on day 8 results in at least about 1,500 ng · h / mL as a result of administration of the dosage form. The method according to any of the above embodiments, wherein the C _max of the threohydroxypropion on day 8 is at least about 600 ng / mL as a result of administration of the dosage form. The method according to any of the above embodiments, wherein the AUC _0-12 of the treohydroxybupropion on day 8 results in at least about 5,000 ng · h / mL as a result of administration of the dosage form.