WO2007114978A2 - Method for treating hiv infection through co-administration of tipranavir and pa-457 - Google Patents
Method for treating hiv infection through co-administration of tipranavir and pa-457 Download PDFInfo
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- WO2007114978A2 WO2007114978A2 PCT/US2007/061589 US2007061589W WO2007114978A2 WO 2007114978 A2 WO2007114978 A2 WO 2007114978A2 US 2007061589 W US2007061589 W US 2007061589W WO 2007114978 A2 WO2007114978 A2 WO 2007114978A2
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- WIPO (PCT)
- Prior art keywords
- tipranavir
- administration
- hiv infection
- ritonavir
- treating hiv
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
Definitions
- TECHNICAL FIELD The present invention relates to a method for treating HIV infection through coadministration of tipranavir and PA-457.
- Tipranavir (also known as PNU 140690) is a non-peptidic HIV protease inhibitor which is useful for the treatment of HIV infection. Tipranavir has the following structural formula,
- 2-Pyridinesulfonamide N-[3-[l-[5,6-dihydro-4-hydroxy-2-oxo-6-(2- phenylethyl)-6- propyl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-, [R-(R* ,R*)]- (Other CA INDEX NAME) 3'-[(lR)-l-[(6R)-5,6-Dihydro-4-hydroxy-2-oxo-6-phenylethyl-6-propyl-2H-pyran-
- tipranavir The synthesis of tipranavir and the manner in which it may be used to treat HIV infection are described in U.S. Patent 5,852,195 and published International Application WO9530670.
- PA-457 also known as YK-FH-312 and PA-103001-01, is an HIV maturation inhibitor (which works by disruption of the processing of the viral capsid- spacer peptide 1 protein) and is useful for the treatment of HIV infection.
- PA-457 has the following chemical structure:
- PA-457 The synthesis of PA-457 and the manner in which it may be used to treat HIV infection are described in published International Application WO009639033.
- Ritonavir is an HIV protease inhibitor. Chemically it is ((2S,3S,5S)-5-(N-(N-((N-Methyl- N-((2-isopropyl-4-thiazoly)methyl)amino)carbonyl)valinyl)amino)-2-(N-((5- thiazoly)methoxycarbonyl) amino)- l,6-diphenyl-3-hydroxyhexane). It has the following structural formula.
- Ritonavir is currently marketed only by Abbott Laboratories, as Norvir® capsules and oral solution.
- the synthesis of Ritonavir is described by U.S. Patent 5,541,206 and granted European Patent EP 0 674 513 Bl.
- Ritonavir is a known inhibitor of Cytochrome P450 monooxygenase (hereinafter called "CYP"). While not approved for this purpose, ritonavir can thus be used to improve the pharmacokinetics of other drugs which are metabolized by CYP.
- CYP Cytochrome P450 monooxygenase
- ritonavir can thus be used to improve the pharmacokinetics of other drugs which are metabolized by CYP.
- Such use is described by U.S. Patent 6,037,157 and the corresponding WO9701349.
- the use ritonavir for the purpose of improving the pharmacokinetics of tipranavir is described in US Patent 6,147,095 and the corresponding WO0025
- the invention provides an improved method for the treatment of HIV infection, especially infection by HIV-I, wherein tipranavir and PA-457 are co-administered.
- the invention further comprises pharmaceutical compositions comprising both tipranavir and PA-457 in a single dosage form.
- a patient suffering from HIV infection is treated for such infection by means of the co-administration of tipranavir and PA-457, optionally in further co-administration with additional anti-viral agents.
- tipranavir and PA-457 may be coadministered by way of separate dosage forms or they may optionally be combined in a single dosage form and administered simultaneously by this means.
- tipranavir is co-administered not only with PA-457 but also with an inhibitor of Cytochrome P450 monooxygenase (hereinafter called "CYP").
- CYP Cytochrome P450 monooxygenase
- the amount of the CYP inhibitor administered should be sufficient to inhibit the metabolism of tipranavir by CYP and thereby facilitate attainment of a therapeutically effective blood level of tipranavir.
- the preferred CYP inhibitor for this purpose is ritonavir, which may be employed in the manner described by U.S. Patent 6,147,095 and the corresponding WO0025784.
- the invention also includes pharmaceutical compositions comprising both tipranavir and PA-457, optionally in further combination with a CYP inhibitor, preferably ritonavir, as a single dosage form.
- the invention further includes is a kit of parts comprising at least two dosage forms, one comprising tipranavir and the other PA-457, wherein the kit optionally further includes a third dosage form comprising a CYP inhibitor, preferably ritonavir.
- tipranavir, PA-457 and CYP inhibitors, particularly ritonavir into appropriate pharmaceutical dosage forms.
- the dosage forms include oral formulations, such as tablets or capsules, or parenteral formulations, such as sterile solutions.
- tipranavir For tipranavir, the most convenient and therefore preferable route of administration will be the oral route. Dosage forms suitable for the oral administration of tipranavir are known per se, having been described by U.S. Patent 5,852,195 and published International Application WO9530670. Exemplary fill formulations for soft gelatin capsules are described by US Patent 6,231,887, WO9906024, WO9906043 and WO9906044.
- tipranavir When tipranavir is to be administered orally, an effective amount is from about 0.1 mg to 100 mg per kg of body weight per day. For adults, the preferred orally-administered dose of tipranavir is 500 mg, co-administered with 200 mg low-dose ritonavir, twice daily. Commercially available ritonavir, such as that sold by Abbott Laboratories under the brand name Norvir®, may be used.
- PA-457 the most convenient and therefore preferable route of administration will also be the oral route.
- Dosage forms suitable for the oral administration of PA-457 are known per se, having been described by published International Application WO009639033.
- an effective daily amount of PA-457 would be from 0.1 mg/kg to 100 mg/kg body weight, more preferably from 1 mg/kg to 100 mg/kg body weight, and most preferably from 10 mg/kg to 100 mg/kg body weight.
- tipranavir with co-administered CYP inhibitor such as ritonavir
- PA-457 as well as any additionally co-administered antiviral agents would be readily determined by those skilled in the art and would be dependant on the age, weight, general physical condition, or other clinical symptoms specific to the patient to be treated.
- the co -administration of tipranavir, CYP inhibitor and PA-457 in accordance with the invention may be accompanied by the further co-administration of additional antiviral agents.
- Said other antiretroviral compounds may be known antiretroviral compounds such as nucleoside reverse transcriptase inhibitors, e.g.
- zidovudine (3'-azido-3'- deoxythymidine, AZT), didanosine (dideoxy inosine; ddl), zalcitabine (dideoxycytidine, ddC) or lamivudine (3 '-thia-2'-3 '-dideoxycytidine, 3TC) and the like; non-nucleoside reverse transciptase inhibitors such as suramine, pentamidine, thymopentin, castanospermine, efavirenz, dextran (dextran sulfate), foscarnet-sodium (trisodium phosphono formate), nevirapine (l l-cyclopropyl-5,l l-dihydro-4-methyl-6H-dipyrido[3,- 2-b: 2', 3'-e][l,4]diazepin-6-one), tacrine (tetrahydroaminoacrid
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
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- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A method for treating HIV infection through co-administration of tipranavir and PA-457.
Description
Method for Treating HIV Infection Through Co- Administration of Tipranavir and PA-457
CROSS-REFERENCE TO RELATED APPLICATIONS The benefit of US Provisional Patent Application No. 60/743,262 filed on February 9, 2006 is hereby claimed.
BACKGROUND OF THE INVENTION
1. TECHNICAL FIELD The present invention relates to a method for treating HIV infection through coadministration of tipranavir and PA-457.
2. BACKGROUND INFORMATION
Tipranavir (also known as PNU 140690) is a non-peptidic HIV protease inhibitor which is useful for the treatment of HIV infection. Tipranavir has the following structural formula,
2-Pyridinesulfonamide, N-[3-[(lR)-l-[(6R)-5,6-dihydro-4-hydroxy-2-oxo-6-(2- phenylethyl)-6-propyl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)- (Preferred CA INDEX NAME)
2-Pyridinesulfonamide, N-[3-[l-[5,6-dihydro-4-hydroxy-2-oxo-6-(2- phenylethyl)-6- propyl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-, [R-(R* ,R*)]- (Other CA INDEX NAME)
3'-[(lR)-l-[(6R)-5,6-Dihydro-4-hydroxy-2-oxo-6-phenylethyl-6-propyl-2H-pyran-
3yl]propyl]-5-(trifluoromethyl)-2-pyridinesulfonanilide
(USP Dictionary of USAN and International Drug Names, 2004 Ed.).
The synthesis of tipranavir and the manner in which it may be used to treat HIV infection are described in U.S. Patent 5,852,195 and published International Application WO9530670.
PA-457, also known as YK-FH-312 and PA-103001-01, is an HIV maturation inhibitor (which works by disruption of the processing of the viral capsid- spacer peptide 1 protein) and is useful for the treatment of HIV infection. PA-457 has the following chemical structure:
The synthesis of PA-457 and the manner in which it may be used to treat HIV infection are described in published International Application WO009639033.
Ritonavir is an HIV protease inhibitor. Chemically it is ((2S,3S,5S)-5-(N-(N-((N-Methyl- N-((2-isopropyl-4-thiazoly)methyl)amino)carbonyl)valinyl)amino)-2-(N-((5- thiazoly)methoxycarbonyl) amino)- l,6-diphenyl-3-hydroxyhexane). It has the following structural formula.
Ritonavir is currently marketed only by Abbott Laboratories, as Norvir® capsules and oral solution. The synthesis of Ritonavir is described by U.S. Patent 5,541,206 and granted European Patent EP 0 674 513 Bl. Ritonavir is a known inhibitor of Cytochrome P450 monooxygenase (hereinafter called "CYP"). While not approved for this purpose, ritonavir can thus be used to improve the pharmacokinetics of other drugs which are metabolized by CYP. Such use is described by U.S. Patent 6,037,157 and the corresponding WO9701349. The use ritonavir for the purpose of improving the pharmacokinetics of tipranavir is described in US Patent 6,147,095 and the corresponding WO0025784.
BRIEF SUMMARY OF THE INVENTION
The invention provides an improved method for the treatment of HIV infection, especially infection by HIV-I, wherein tipranavir and PA-457 are co-administered. The invention further comprises pharmaceutical compositions comprising both tipranavir and PA-457 in a single dosage form.
DETAILED DESCRIPTION OF THE INVENTION In accordance with the invention, a patient suffering from HIV infection, especially infection by HIV-I, is treated for such infection by means of the co-administration of tipranavir and PA-457, optionally in further co-administration with additional anti-viral agents.
-3-
For the purpose of carrying out the invention, tipranavir and PA-457 may be coadministered by way of separate dosage forms or they may optionally be combined in a single dosage form and administered simultaneously by this means.
Preferably, in accordance with the invention, tipranavir is co-administered not only with PA-457 but also with an inhibitor of Cytochrome P450 monooxygenase (hereinafter called "CYP"). The amount of the CYP inhibitor administered should be sufficient to inhibit the metabolism of tipranavir by CYP and thereby facilitate attainment of a therapeutically effective blood level of tipranavir. The preferred CYP inhibitor for this purpose is ritonavir, which may be employed in the manner described by U.S. Patent 6,147,095 and the corresponding WO0025784.
The invention also includes pharmaceutical compositions comprising both tipranavir and PA-457, optionally in further combination with a CYP inhibitor, preferably ritonavir, as a single dosage form. The invention further includes is a kit of parts comprising at least two dosage forms, one comprising tipranavir and the other PA-457, wherein the kit optionally further includes a third dosage form comprising a CYP inhibitor, preferably ritonavir.
Those skilled in the art will know how to formulate tipranavir, PA-457 and CYP inhibitors, particularly ritonavir, into appropriate pharmaceutical dosage forms. Examples of the dosage forms include oral formulations, such as tablets or capsules, or parenteral formulations, such as sterile solutions.
For tipranavir, the most convenient and therefore preferable route of administration will be the oral route. Dosage forms suitable for the oral administration of tipranavir are known per se, having been described by U.S. Patent 5,852,195 and published International Application WO9530670. Exemplary fill formulations for soft gelatin capsules are described by US Patent 6,231,887, WO9906024, WO9906043 and WO9906044.
When tipranavir is to be administered orally, an effective amount is from about 0.1 mg to 100 mg per kg of body weight per day. For adults, the preferred orally-administered dose
of tipranavir is 500 mg, co-administered with 200 mg low-dose ritonavir, twice daily. Commercially available ritonavir, such as that sold by Abbott Laboratories under the brand name Norvir®, may be used.
For PA-457, the most convenient and therefore preferable route of administration will also be the oral route. Dosage forms suitable for the oral administration of PA-457 are known per se, having been described by published International Application WO009639033. In general, for the purpose of practicing the present invention, an effective daily amount of PA-457 would be from 0.1 mg/kg to 100 mg/kg body weight, more preferably from 1 mg/kg to 100 mg/kg body weight, and most preferably from 10 mg/kg to 100 mg/kg body weight.
The exact route of administration, dose, or frequency of administration of tipranavir (with co-administered CYP inhibitor such as ritonavir) and PA-457, as well as any additionally co-administered antiviral agents would be readily determined by those skilled in the art and would be dependant on the age, weight, general physical condition, or other clinical symptoms specific to the patient to be treated.
Optionally, the co -administration of tipranavir, CYP inhibitor and PA-457 in accordance with the invention may be accompanied by the further co-administration of additional antiviral agents. Said other antiretroviral compounds may be known antiretroviral compounds such as nucleoside reverse transcriptase inhibitors, e.g. zidovudine (3'-azido-3'- deoxythymidine, AZT), didanosine (dideoxy inosine; ddl), zalcitabine (dideoxycytidine, ddC) or lamivudine (3 '-thia-2'-3 '-dideoxycytidine, 3TC) and the like; non-nucleoside reverse transciptase inhibitors such as suramine, pentamidine, thymopentin, castanospermine, efavirenz, dextran (dextran sulfate), foscarnet-sodium (trisodium phosphono formate), nevirapine (l l-cyclopropyl-5,l l-dihydro-4-methyl-6H-dipyrido[3,- 2-b: 2', 3'-e][l,4]diazepin-6-one), tacrine (tetrahydroaminoacridine) and the like; compounds of the TIBO (tetrahydro-imidazo[4,5,l-jk][l,4]-benzodiazepine-2(lH)-one and thione)-type e.g. (S)-8-chloro-4,5,6,7-tetrahydro-5- -methyl-6-(3-methyl-2- butenyl)imidazo-[4,5,l-jk][l,4]benzodiazepine-2(lH)-thione; compounds of the .alpha.-
APA (. alpha. -anilino phenyl acetamide) type e.g. .alpha.-[(2-nitro-phenyl)amino]-2,6- dichlorobenzene-acetamide and the like; TAT -inhibitors, e.g. RO-5-3335 and the like; protease inhibitors e.g. indinavir, saquinovir, ABT-378 and the like; or immunomodulatin^ agents, e.g. levamisole and the like.
Claims
1. A method for treating HIV infection which comprises co-administering tipranavir and PA-457 in therapeutically effective amounts.
2. The use of tipranavir and PA-457 in the manufacture of a medicament for the treatment of HIV infection.
3. A pharmaceutical composition comprising tipranavir and PA-457 and a pharmaceutically acceptable carrier.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US74326206P | 2006-02-09 | 2006-02-09 | |
US60/743,262 | 2006-02-09 |
Publications (2)
Publication Number | Publication Date |
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WO2007114978A2 true WO2007114978A2 (en) | 2007-10-11 |
WO2007114978A3 WO2007114978A3 (en) | 2008-04-17 |
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PCT/US2007/061589 WO2007114978A2 (en) | 2006-02-09 | 2007-02-05 | Method for treating hiv infection through co-administration of tipranavir and pa-457 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009090063A1 (en) * | 2008-01-16 | 2009-07-23 | Jado Technologies Gmbh | Steroid sapogenin, androstane and triterpenoid sapogenin derivatives for the treatment and prevention of infectious diseases |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996039033A1 (en) * | 1995-06-05 | 1996-12-12 | The University Of North Carolina At Chapel Hill | Betulinic acid derivatives and uses therefor |
WO2004087139A1 (en) * | 2003-03-27 | 2004-10-14 | Boehringer Ingelheim International Gmbh | Antiviral combination of tipranavir and a further antiretroviral compound |
US20050131017A1 (en) * | 2003-12-11 | 2005-06-16 | Degoey David A. | HIV protease inhibiting compounds |
-
2007
- 2007-02-05 WO PCT/US2007/061589 patent/WO2007114978A2/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996039033A1 (en) * | 1995-06-05 | 1996-12-12 | The University Of North Carolina At Chapel Hill | Betulinic acid derivatives and uses therefor |
WO2004087139A1 (en) * | 2003-03-27 | 2004-10-14 | Boehringer Ingelheim International Gmbh | Antiviral combination of tipranavir and a further antiretroviral compound |
US20050131017A1 (en) * | 2003-12-11 | 2005-06-16 | Degoey David A. | HIV protease inhibiting compounds |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009090063A1 (en) * | 2008-01-16 | 2009-07-23 | Jado Technologies Gmbh | Steroid sapogenin, androstane and triterpenoid sapogenin derivatives for the treatment and prevention of infectious diseases |
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WO2007114978A3 (en) | 2008-04-17 |
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