CA2346131C - Method for improving the pharmacokinetics of tipranavir - Google Patents
Method for improving the pharmacokinetics of tipranavir Download PDFInfo
- Publication number
- CA2346131C CA2346131C CA2346131A CA2346131A CA2346131C CA 2346131 C CA2346131 C CA 2346131C CA 2346131 A CA2346131 A CA 2346131A CA 2346131 A CA2346131 A CA 2346131A CA 2346131 C CA2346131 C CA 2346131C
- Authority
- CA
- Canada
- Prior art keywords
- tipranavir
- ritonavir
- bid
- concentrations
- plasma
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 title claims abstract description 273
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 title claims abstract description 271
- 229960000838 tipranavir Drugs 0.000 title claims abstract description 271
- 238000000034 method Methods 0.000 title abstract description 36
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims abstract description 205
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims abstract description 198
- 229960000311 ritonavir Drugs 0.000 claims abstract description 192
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 abstract description 21
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 102
- 229960005319 delavirdine Drugs 0.000 description 48
- 229940079593 drug Drugs 0.000 description 37
- 239000003814 drug Substances 0.000 description 37
- 230000000694 effects Effects 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 230000001965 increasing effect Effects 0.000 description 23
- 208000030507 AIDS Diseases 0.000 description 19
- 241000725303 Human immunodeficiency virus Species 0.000 description 19
- 239000000203 mixture Substances 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000008406 drug-drug interaction Effects 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- 108091005804 Peptidases Proteins 0.000 description 12
- 102000035195 Peptidases Human genes 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 229940088598 enzyme Drugs 0.000 description 12
- 229940096357 ritonavir 100 mg Drugs 0.000 description 12
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 11
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 208000031886 HIV Infections Diseases 0.000 description 10
- 239000004365 Protease Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 235000019419 proteases Nutrition 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 241001430294 unidentified retrovirus Species 0.000 description 9
- 239000002775 capsule Substances 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 230000036470 plasma concentration Effects 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 230000036765 blood level Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 108010010369 HIV Protease Proteins 0.000 description 6
- 208000037357 HIV infectious disease Diseases 0.000 description 6
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 229940072586 ritonavir oral solution Drugs 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 5
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000000840 anti-viral effect Effects 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000011260 co-administration Methods 0.000 description 4
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000001524 infective effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 4
- 229960002555 zidovudine Drugs 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
- 206010013710 Drug interaction Diseases 0.000 description 3
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 3
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 229940124522 antiretrovirals Drugs 0.000 description 3
- 239000008135 aqueous vehicle Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 229940072250 norvir Drugs 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 3
- 229960001225 rifampicin Drugs 0.000 description 3
- -1 ritonavir Chemical compound 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XTYSXGHMTNTKFH-BDEHJDMKSA-N (2s)-1-[(2s,4r)-4-benzyl-2-hydroxy-5-[[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;hydrate Chemical compound O.C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 XTYSXGHMTNTKFH-BDEHJDMKSA-N 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- 241000220479 Acacia Species 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003903 antiretrovirus agent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 231100000676 disease causative agent Toxicity 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000004030 hiv protease inhibitor Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229960001936 indinavir Drugs 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 2
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- AHNZDDRXVDLYMH-UHFFFAOYSA-N (5-hydroxy-1h-indol-2-yl)-[4-[3-(propan-2-ylamino)pyridin-2-yl]piperazin-1-yl]methanone Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(O)C=C3C=2)CC1 AHNZDDRXVDLYMH-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003581 Asymptomatic HIV infection Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 210000004366 CD4-positive T-lymphocyte Anatomy 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 229940122440 HIV protease inhibitor Drugs 0.000 description 1
- 206010020144 Histoplasmosis disseminated Diseases 0.000 description 1
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101710198130 NADPH-cytochrome P450 reductase Proteins 0.000 description 1
- 229940124821 NNRTIs Drugs 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 101150053185 P450 gene Proteins 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- ZWBTYMGEBZUQTK-PVLSIAFMSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,23-dioxospiro[8,33-dioxa-24,27,29-triazapentacyclo[23.6.1.14,7.05,31.026,30]tritriaconta-1(32),2,4,9,19,21,24,26,30-nonaene-28,4'-piperidine]-13-yl] acetate Chemical compound CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c2c4NC5(CCN(CC(C)C)CC5)N=c4c(=NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(O)c2c(O)c3C ZWBTYMGEBZUQTK-PVLSIAFMSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ZBWMQTUSVWBMQE-KPHXKKTMSA-M disodium;(2r)-4-oxo-2-(2-phenylethyl)-2-propyl-5-[(1r)-1-[3-[5-(trifluoromethyl)pyridin-2-yl]sulfonylazanidylphenyl]propyl]-3h-pyran-6-olate Chemical class [Na+].[Na+].C([C@@]1(CCC)OC([O-])=C([C@H](CC)C=2C=C([N-]S(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)C1)CC1=CC=CC=C1 ZBWMQTUSVWBMQE-KPHXKKTMSA-M 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 238000002552 multiple reaction monitoring Methods 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229960000689 nevirapine Drugs 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229940063627 rescriptor Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960000885 rifabutin Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000007501 viral attachment Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000029302 virus maturation Effects 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- 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)
- Virology (AREA)
- Epidemiology (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10696398P | 1998-11-04 | 1998-11-04 | |
| US60/106,963 | 1998-11-04 | ||
| PCT/US1999/021469 WO2000025784A1 (en) | 1998-11-04 | 1999-10-29 | Method for improving the pharmacokinetics of tipranavir |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2346131A1 CA2346131A1 (en) | 2000-05-11 |
| CA2346131C true CA2346131C (en) | 2013-01-15 |
Family
ID=22314155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2346131A Expired - Lifetime CA2346131C (en) | 1998-11-04 | 1999-10-29 | Method for improving the pharmacokinetics of tipranavir |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6147095A (enExample) |
| EP (1) | EP1126847A1 (enExample) |
| JP (1) | JP2002528502A (enExample) |
| CN (1) | CN1154491C (enExample) |
| AU (1) | AU762349B2 (enExample) |
| BR (1) | BR9914940A (enExample) |
| CA (1) | CA2346131C (enExample) |
| CO (1) | CO5160321A1 (enExample) |
| HK (1) | HK1040625B (enExample) |
| MY (1) | MY118526A (enExample) |
| PE (1) | PE20001296A1 (enExample) |
| TW (1) | TW580387B (enExample) |
| WO (1) | WO2000025784A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9815567D0 (en) * | 1998-07-18 | 1998-09-16 | Glaxo Group Ltd | Antiviral compound |
| ES2298286T3 (es) * | 2000-10-31 | 2008-05-16 | Boehringer Ingelheim Pharmaceuticals Inc. | Formulaciones de dosis orales auto-emulsionantes de inhibidores de proteasa de piranona. |
| DE10108470A1 (de) * | 2001-02-22 | 2002-09-05 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung optisch aktiver Dihydropyrone |
| US6500963B2 (en) | 2001-02-22 | 2002-12-31 | Boehringer Ingelheim Pharma Kg | Process for preparing optically active dihydropyrones |
| US20040197321A1 (en) * | 2002-03-19 | 2004-10-07 | Tibor Sipos | Composition and method to prevent or reduce diarrhea and steatorrhea in HIV patients |
| US20030180279A1 (en) * | 2002-03-19 | 2003-09-25 | Tibor Sipos | Composition and method to prevent or reduce diarrhea and steatorrhea in HIV patients |
| KR20050085681A (ko) * | 2002-12-16 | 2005-08-29 | 베링거 인겔하임 인터내셔날 게엠베하 | 프로테아제 억제제와 같은 사이토크롬 ｐ450의 억제제와함께 비-뉴클레오시드 역전사효소 억제제(ｎｎｒｔｉ)를함유하는 배합물의 용도 |
| AU2003295940A1 (en) * | 2002-12-16 | 2004-07-29 | Boehringer Ingelheim Pharmaceuticals, Inc. | Treatment of hiv infection through combined administration of tipranavir and capravirine |
| EP1610781A1 (en) * | 2003-03-27 | 2006-01-04 | Boehringer Ingelheim International GmbH | Antiviral combination of tipranavir and a further antiretroviral compound |
| AR045841A1 (es) * | 2004-09-28 | 2005-11-16 | Richmond Sa Com Ind Y Financie | Una composicion farmaceutica solida que comprende al tiazolil metil ester del acido [5s-(5r*, 8r*, 10r*,11r*)] -10- hidroxi-2- metil-5-(1-metiletil)-1-[2-(1-metiletil)-4-tiazolil]-3,6-dioxo-8,11-bis(fenilmetil)-2,4,7,12- tetraazatridecan-13-oico y un procedimiento para prepararla. |
| EP1812069A2 (en) * | 2004-11-08 | 2007-08-01 | Boehringer Ingelheim International GmbH | Method for treating hiv infection through co-administration of tipranavir and etravirine |
| US20060135562A1 (en) * | 2004-11-16 | 2006-06-22 | Boehringer Ingelheim International Gmbh | Method for treating HIV infection through co-administration of tipranavir and darunavir |
| EP1814549A2 (en) * | 2004-11-19 | 2007-08-08 | Boehringer Ingelheim International GmbH | Method for treating hiv infection through co-administration of tipranavir and uk-427, 857 |
| US20060128733A1 (en) * | 2004-11-19 | 2006-06-15 | Boehringer Ingelheim International Gmbh | Method for treating HIV infection through co-administration of tipranavir and reverset |
| WO2006060175A1 (en) * | 2004-12-01 | 2006-06-08 | Boehringer Ingelheim International Gmbh | Method for treating hiv infection through co-administration of tipranavir and sch-417690 |
| WO2006060177A1 (en) * | 2004-12-01 | 2006-06-08 | Boehringer Ingelheim International Gmbh | Method for treating hiv infection through co-administration of tipranavir and gw873140 |
| JP2008521896A (ja) * | 2004-12-01 | 2008-06-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | チプラナビル及びｇｗ６９５６３４を共に投与することを含むｈｉｖ感染症の治療方法 |
| WO2008112289A2 (en) | 2007-03-12 | 2008-09-18 | Nektar Therapeutics | Oligomer-protease inhibitor conjugates |
| WO2009114151A1 (en) * | 2008-03-12 | 2009-09-17 | Nektar Therapeutics | Oligomer-amino acid and olgomer-atazanavir conjugates |
| US20100021505A1 (en) * | 2008-07-28 | 2010-01-28 | Tibor Sipos | Composition and method to prevent or reduce diarrhea and steatorrhea in HIV patients |
| EP2440249A2 (en) | 2009-06-12 | 2012-04-18 | Nektar Therapeutics | Covalent conjugates comprising a protease inhibitor, a water-soluble, non-peptidic oligomer and a lipophilic moiety |
| MX2012011415A (es) * | 2010-04-02 | 2013-02-26 | Phivco 1 Llc | Terapia de combinacion que comprende un antagonista de ccr5, un inhibidor de proteasa de vih-1, y un potenciador farmacocinetico. |
| AU2012262322B2 (en) * | 2011-05-30 | 2016-11-03 | Autotelic Llc | Methods and compositions for therapeutic drug monitoring and dosing by point-of-care pharmacokinetic profiling |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5608085A (en) * | 1995-02-27 | 1997-03-04 | The University Of Tennessee Research Corporation | Synthesis of optically active calanolides A and B and enantiomers and related compounds |
| US6037157A (en) * | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| US5932570A (en) * | 1996-11-08 | 1999-08-03 | Dupont Pharmaceuticals Company | 1-(3-aminoindazol-5-yl)-3-phenylmethyl-cyclic ureas useful as HIV protease inhibitors |
| ZA9710071B (en) * | 1996-11-21 | 1998-05-25 | Abbott Lab | Pharmaceutical composition. |
-
1999
- 1999-10-29 HK HK02102194.8A patent/HK1040625B/zh not_active IP Right Cessation
- 1999-10-29 US US09/430,742 patent/US6147095A/en not_active Expired - Lifetime
- 1999-10-29 JP JP2000579225A patent/JP2002528502A/ja active Pending
- 1999-10-29 WO PCT/US1999/021469 patent/WO2000025784A1/en not_active Ceased
- 1999-10-29 EP EP99971319A patent/EP1126847A1/en active Pending
- 1999-10-29 AU AU14404/00A patent/AU762349B2/en not_active Expired
- 1999-10-29 CN CNB998123587A patent/CN1154491C/zh not_active Expired - Lifetime
- 1999-10-29 CA CA2346131A patent/CA2346131C/en not_active Expired - Lifetime
- 1999-10-29 BR BR9914940-0A patent/BR9914940A/pt not_active Application Discontinuation
- 1999-11-03 PE PE1999001100A patent/PE20001296A1/es not_active Application Discontinuation
- 1999-11-04 MY MYPI99004794A patent/MY118526A/en unknown
- 1999-11-04 CO CO99069669A patent/CO5160321A1/es unknown
- 1999-11-04 TW TW088119229A patent/TW580387B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002528502A (ja) | 2002-09-03 |
| CO5160321A1 (es) | 2002-05-30 |
| EP1126847A1 (en) | 2001-08-29 |
| CN1154491C (zh) | 2004-06-23 |
| CN1324237A (zh) | 2001-11-28 |
| BR9914940A (pt) | 2001-07-10 |
| PE20001296A1 (es) | 2000-11-23 |
| CA2346131A1 (en) | 2000-05-11 |
| WO2000025784A1 (en) | 2000-05-11 |
| AU762349B2 (en) | 2003-06-26 |
| MY118526A (en) | 2004-11-30 |
| TW580387B (en) | 2004-03-21 |
| AU1440400A (en) | 2000-05-22 |
| HK1040625B (zh) | 2005-04-01 |
| US6147095A (en) | 2000-11-14 |
| HK1040625A1 (en) | 2002-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6147095A (en) | Method for improving the pharmacokinetics of tipranavir | |
| Noble et al. | Saquinavir: a review of its pharmacology and clinical potential in the management of HIV infection | |
| US20110003764A1 (en) | Methods for Treatment of HIV or Malaria Using Combinations of Chloroquine and Protease Inhibitors | |
| US20080096832A1 (en) | Method for Improving the Pharmacokinetics of an NNRTI | |
| KR20100040892A (ko) | 치료 조성물 및 그의 용도 | |
| Kageyama et al. | In vitro inhibition of human immunodeficiency virus (HIV) type 1 replication by C2 symmetry-based HIV protease inhibitors as single agents or in combinations | |
| Craig et al. | Antiviral synergy between inhibitors of HIV proteinase and reverse transcriptase | |
| Lazdins et al. | In vitro effect of α1-acid glycoprotein on the anti-human immunodeficiency virus (HIV) activity of the protease inhibitor CGP 61755: a comparative study with other relevant HIV protease inhibitors | |
| Ghosh et al. | Antiviral activity of UIC-PI, a novel inhibitor of the human immunodeficiency virus type 1 protease | |
| Dianzani et al. | In vitro selection of human immunodeficiency virus type 1 resistant to Ro 31-8959 proteinase inhibitor | |
| Lambert et al. | Synergistic drug interactions of an HIV-1 protease inhibitor with AZT in different in vitro models of HIV-1 infection | |
| EP1712231A2 (en) | Method for improving the pharmacokinetics of tipranavir | |
| Kubin et al. | Antiretroviral agents | |
| Taylor et al. | Synergistic inhibition of human immunodeficiency virus type 1 in vitro by 6-0-butanoylcastanospermine (MDL 28574) in combination with inhibitors of the virus-encoded reverse transcriptase and proteinase | |
| Chokekijchai et al. | In vitro anti-HIV-1 activity of HIV protease inhibitor KNI-272 in resting and activated cells: implications for its combined use with AZT or ddI | |
| WO2005000405A2 (en) | P38 kinase inhibitor compositions and methods of use | |
| Stanic et al. | Review of antiretroviral agents for the treatment of HIV infection. | |
| Kahn | The clinical use of didanosine | |
| Redshaw et al. | Human Immunodeficiency Virus Protease Inhibitors | |
| CN1901914B (zh) | 包含喹啉抗疟化合物和蛋白酶抑制剂的组合的药物组合物及其应用 | |
| AU2008201715B2 (en) | Methods for treatment of HIV or malaria using combinations of chloroquine and protease inhibitors | |
| Abd-Elazem | Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase and viral replication | |
| Fritsch et al. | Anti-retroviral therapy in HIV-1-infected persons: Concepts and strategies | |
| Dukes et al. | Potent inhibition of HIV type 1 infection of mononuclear phagocytes by synthetic peptide analogs of HIV type 1 protease substrates | |
| Rusconi | Tipranavir |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20191029 |