WO2005009432A1 - Posologie nouvelle en cas d'administration concurrente de gabapentine avec des aliments et biodisponibilite orale accrue ainsi obtenue - Google Patents

Posologie nouvelle en cas d'administration concurrente de gabapentine avec des aliments et biodisponibilite orale accrue ainsi obtenue Download PDF

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Publication number
WO2005009432A1
WO2005009432A1 PCT/IB2004/051334 IB2004051334W WO2005009432A1 WO 2005009432 A1 WO2005009432 A1 WO 2005009432A1 IB 2004051334 W IB2004051334 W IB 2004051334W WO 2005009432 A1 WO2005009432 A1 WO 2005009432A1
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WO
WIPO (PCT)
Prior art keywords
gabapentin
dosage form
food
oral
hour
Prior art date
Application number
PCT/IB2004/051334
Other languages
English (en)
Inventor
Manish Chawla
Rajeev Singh Raghuvanshi
Ashok Rampal
Original Assignee
Ranbaxy Laboratories Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2005009432A1 publication Critical patent/WO2005009432A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group

Definitions

  • the present invention relates to methods of increasing the oral bioavailability of gabapentin.
  • Gabapentin (l-(aminomethyl)cyclohexaneacetic acid) is a #-amino acid analogue effective in the treatment of epilepsy. Gabapentin is indicated as an adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy. Gabapentin has also been approved for neuropathic pain in some countries.
  • Gabapentin has shown to exert its anti-seizure activity in mice and rats in both maximal electroshock and pentylenetetrazole seizures, but the mechanism of action of gabapentin against seizures is unknown. What is known is that Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but does not interact with GABA receptor. It is not converted to GABA or a GABA agonist and is not an inhibitor of GABA uptake or degradation.
  • GABA gamma-aminobutyric acid
  • Gabapentin has a relatively short half-life (5-7 hours), which leads to substantial fluctuations in the plasma concentration of the drug. Frequent dosing is necessary to maintain reasonably stable plasma concentrations.
  • the effective dose of gabapentin is 900 to 1800 mg/day and is given three times a day.
  • Gabapentin is typically absorbed from the upper intestine, i.e., it has a narrow absorption window and is absorbed by active transport through a large neutral amino acid (LNAA) transporter. This transporter is located in upper small intestine and has limited transport capacity and becomes saturated when exposed to high drug concentrations. Consequently, the plasma levels of gabapentin are not dose proportional and, therefore, higher doses do not give proportionately higher plasma levels. This fact also explains the poor oral bioavailability of gabapentin even when the dose is increased.
  • LNAA neutral amino acid
  • a method of treating a patient for a condition for which gabapentin is indicated includes administering a controlled release oral dosage form comprising a therapeutically effective amount of gabapentin, the gabapentin dosage form being indicated for once daily administration; and consuming food within one hour of administering the oral dosage form.
  • Embodiments of the method may include one or more of the following features.
  • administering the dosage form within one hour of consuming food may increase the extent of absorption of gabapentin in the patient.
  • Administering the dosage form within one hour of consuming food may increase the oral bioavailability of gabapentin in the patient.
  • Administering the dosage form within one hour of consuming food may reduces the per day dosing frequency of the gabapentin by increasing the oral bioavailability of gabapentin in the patient, and the dosing frequency may be reduced from twice daily to once daily.
  • Administering the dosage form within one hour of consuming food may reduce the daily dose of gabapentin to the patient.
  • the oral dosage form may be one or more of tablets, capsules, granules, solid dosage form, or oral liquid dosage form.
  • the oral dosage form may be a sustained release dosage form.
  • the oral dosage form may be administered within 20 minutes to one hour of the consumption of food.
  • the oral dosage form may be administered at the same time as the consumption of food.
  • the oral dosage form may be administered at a time ranging between immediately after consumption of food and up to one hour after the consumption of food.
  • the invention relates to a method of increasing the oral bioavailability of gabapentin by administering a therapeutically effective amount of gabapentin or a pharmaceutically acceptable salt or hydrates thereof in an oral dosage form with food.
  • a dosage form of gabapentin when taken with food, allows for the increased absorption of gabapentin at the specific absorption site.
  • Our studies have revealed that an improvement in oral bioavailability is observed when an oral gabapentin dosage form is administered with food as indicated by the various pharmacokinetic parameters such as C max and AUG.
  • the term 'therapeutically effective amount' refers to an amount which is sufficient to treat a mammal in need of the treatment. Generally, the therapeutically effective amount varies depending upon the subject being treated and upon the medical condition for which the treatment is being given.
  • the method of the present invention involves administering gabapentin with food to a subject as long as the medical condition exists.
  • the term 'gabapentin' as used herein includes gabapentin or a pharmaceutically acceptable salt of hydrates thereof.
  • Non-limiting example include gabapentin hy- drochloride, gabapentin monohydrate or any other pharmaceutically acceptable form known to the skilled in the art.
  • the dose of gabapentin is determined by the medical condition for which the treatment is sought.
  • One aspect of the method of the present invention includes increasing the oral bioavailability of gabapentin for treating the medical condition which is responsive to gabapentin therapy.
  • the dose can be from about 300 - 3600 mg per day, particularly about 900 -2400 mg per day, more particularly about 900 - 1800 mg per day.
  • the dose can be from about 100 - 4800 mg per day, particularly from about 300 - 3600 mg per day, and more particularly from about 900 - 2400 mg per day.
  • the dosage form for delivering gabapentin to a subject is oral.
  • the oral dosage form can be a tablet, capsule or granule or any other solid oral dosage from or an oral liquid dosage form, in which the intended dose may be conveniently delivered to the subject being treated.
  • the dosage form also includes the conventional dosage forms meant for immediate release and sustained release dosage form meant for controlled release of gabapentin.
  • Commercially available dosage forms of gabapentin are also included in the method of the invention.
  • the oral administration of gabapentin with food means that the gabapentin is ingested anywhere within the time period from one hour before the consumption of food to one hour after the consumption of food, as well as at the same time as the consumption of food.
  • gabapentin absorption is more efficient, for a given amount of dose, when administered with food because the chance that the specific LNAA transporter becoming saturated are reduced as a result of the slow feeding of gabapentin from the stomach to the upper regions of intestine over a prolonged period.
  • EXAMPLE 1 An open label, randomized, two-treatment, two period, two sequence, crossover, single dose pharmacokinetic study under fasting (Test A) and fed (Test B) conditions was conducted in 12 healthy human male volunteers with a washout period of 3 days to compare the effect of food on the bioavailability of gabapentin. Fasting state was achieved by overnight fast of at least 10 hours and continued until 4 hours post dose. For fed state the subject was given breakfast and the gabapentin was administered 20 minutes after the breakfast. Each subject was administered gabapentin as a 900 mg sustained release tablet with 240 L of water under both fasting and fed states. Plasma sample were taken from pre-dose to up to 24 hours. The resulting pharmacokinetic data is given in Tables 1-5.
  • Figure 1 is a plot of mean plasma concentration of gabapentin in nanograms per miUiliters versus the time elapsed from administration of the dosage form. Two plots are shown for a 900 mg dosage form administered with and without food.
  • FIG. 1 shows a plot of the mean plasma concentration of gabapentin in nanograms per miUiliters versus the time elapsed administered with and without food.

Abstract

L'invention concerne l'utilisation d'une forme d'administration orale de gabapentine à libération contrôlée pour préparer un médicament à administrer une fois par jour, suivi dans un délai de moins d'une heure par l'absorption d'aliments, afin de traiter des troubles pour le traitement desquels la gabapentine est indiquée.
PCT/IB2004/051334 2003-07-29 2004-07-29 Posologie nouvelle en cas d'administration concurrente de gabapentine avec des aliments et biodisponibilite orale accrue ainsi obtenue WO2005009432A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN940DE2003 2003-07-29
IN940/DEL/2003 2003-07-29

Publications (1)

Publication Number Publication Date
WO2005009432A1 true WO2005009432A1 (fr) 2005-02-03

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Application Number Title Priority Date Filing Date
PCT/IB2004/051334 WO2005009432A1 (fr) 2003-07-29 2004-07-29 Posologie nouvelle en cas d'administration concurrente de gabapentine avec des aliments et biodisponibilite orale accrue ainsi obtenue

Country Status (2)

Country Link
CN (1) CN1832735A (fr)
WO (1) WO2005009432A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI397275B (zh) * 2009-05-18 2013-05-21 Inst Information Industry 用於一多輸入多輸出無線通訊系統之增益調整裝置、方法及其電腦程式產品

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000076478A1 (fr) * 1999-06-14 2000-12-21 Cosmo S.P.A. Compositions pharmaceutiques administrables par voie orale a liberation controlee et gout masque
WO2002028881A1 (fr) * 2000-10-06 2002-04-11 Xenoport, Inc. Composes derives d'acide biliaire assurant des concentrations systemiques prolongees de medicaments apres administration par voie orale
WO2003035040A1 (fr) * 2001-10-25 2003-05-01 Depomed, Inc. Methodes de traitement a l'aide d'un dosage de gabapentine a retenue gastrique

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000076478A1 (fr) * 1999-06-14 2000-12-21 Cosmo S.P.A. Compositions pharmaceutiques administrables par voie orale a liberation controlee et gout masque
WO2002028881A1 (fr) * 2000-10-06 2002-04-11 Xenoport, Inc. Composes derives d'acide biliaire assurant des concentrations systemiques prolongees de medicaments apres administration par voie orale
WO2003035040A1 (fr) * 2001-10-25 2003-05-01 Depomed, Inc. Methodes de traitement a l'aide d'un dosage de gabapentine a retenue gastrique

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI397275B (zh) * 2009-05-18 2013-05-21 Inst Information Industry 用於一多輸入多輸出無線通訊系統之增益調整裝置、方法及其電腦程式產品

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Publication number Publication date
CN1832735A (zh) 2006-09-13

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