Steady-state disposition of the nonpeptidic protease inhibitor tipranavir when coadministered with ritonavir

Antimicrobial Agents and Chemotherapy

Volumn 51, Issue 7, 2007, Pages 2436-2444

  Chen, Linzhi ^a   Sabo, John P ^a   Philip, Elsy ^a   Mao, Yanping ^a   Norris, Stephen H ^a   MacGregor, Thomas R ^a   Wruck, Jan M ^a   Garfinkel, Sandra ^a   Castles, Mark ^a   Brinkman, Amy ^b   Valdez, Hernan ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^b 206 Carnegie Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; CARBON 14; PROTEINASE INHIBITOR; RITONAVIR; TIPRANAVIR;

ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG DISPOSITION; DRUG FECES LEVEL; DRUG GLUCURONIDATION; DRUG METABOLISM; DRUG URINE LEVEL; ERYTHROCYTE; HUMAN; HUMAN EXPERIMENT; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MALE; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PLASMA; PRIORITY JOURNAL; RADIATION DETECTION; SINGLE DRUG DOSE; STEADY STATE; TANDEM MASS SPECTROMETRY; TREATMENT DURATION;

ADMINISTRATION, ORAL; ANTI-HIV AGENTS; CAPSULES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; DRUG SYNERGISM; FECES; HIV PROTEASE INHIBITORS; HUMANS; MALE; PYRIDINES; PYRONES; RITONAVIR;

EID: 34447275664     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.01115-06     Document Type: Article

References (16)

1. Back, N. K. T., A. van Wijk, D. Remmerswaal, M. van Monfort, M. Nijhuis, R. Schuurman, and C. A. B. Boucher. 2000. In-vitro tipranavir susceptibility of HIV-1 isolates with reduced susceptibility to other protease inhibitors. AIDS 14:101-102.
2. Calm, P., J. Villacian, A. Lazzarin, C. Katlama, B. Grinsztejn, K. Arasteh, P. Lopez, N. Clumeck, J. Gerstoft, N. Stavrianeas, S. Moreno, F. Antunes, D. Neubacher, and D. Mayers. 2006. Ritonavir-boosted tipranavir demonstrates superior efficacy to ritonavir-boosted protease inhibitors in treatment-experienced HIV-infected patients: 24-week results of the RESIST-2 trial. Clin. Infect. Dis. 43:1347-1356.
3. Gathe, J., D. A. Cooper, C. Farthing, D. Jayaweera, D. Norris, G. Pierone, C. R. Steinhart, B. Trottier, S. L. Walmsley, C. Workman, G. Mukwaya, V. Kohlbrenner, C. Dohnanyi, S. McCallister, and D. Mayers for the RESIST-1 Study Team. 2006. Efficacy of the protease-inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-week analysis from the RESIST-1 trial. Clin. Infect. Dis. 43:1337-1346.
4. Gathe, J. C., G. Pierone, P. Piliero, K. Arasteh, R. Rubio, R. G. LaLonde, D. Cooper, A. Lazzarin, V. M. Kohlbrenner, C. Dohnanyi, J. Sabo, and D. Mayers. 2007. Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type-1-infected patients. AIDS Res. Hum. Retrovir. 23:216-223.
5. Koudriakova, T., E. Iatsimirskaia, I. Utkin, E. Gangl, P. Vouros, E. Storozhuk, D. Orza, J. Marinina, and N. Gerber. 1998. Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P450 3A4/3A5: mechanism-based inactivation of cytochrome P450 3A by ritonavir. Drug Metab. Dispos. 26:552-561.
6. Larder, B. A., K. Hertogs, S. Bloor, C. van den Eynde, W. DeCian, Y. Wang, W. W. Freimuth, and G. Tarpley. 2000. Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS 14:1943-1948.
7. Lee, C. G. L., M. M. Gottesman, C. O. Cardarelli, M. Ramachandra, K.-T. Jeang, S. V. Ambudkar, I. Pastan, and S. Dey. 1998. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 37:3594-3601.
8. MacGregor, T. R., J. P. Sabo, S. H. Norris, P. Johnson, L. Galitz, and S. McCallister. 2004. Pharmacokinetic characterization of different dose combinations of coadministered tipranavir and ritonavir in healthy volunteers. HIV Clin. Trials 5:371-382.
9. McCallister, S., H. Valdez, K. Curry, T. MacGregor, M. Borin, W. Freimuth, Y. Wang, and D. L. Mayers. 2004. 14-day dose-response study of the efficacy, safety, and pharmacokinetics of the nonpeptidic protease inhibitor tipranavir in treatment-naive HIV-1-infected patients. J. Acquir. Immune Defic. Syndr. 35:376-382.
10. Monini, P., C. Sgadari, G. Barillari, and B. Ensoli. 2003. HIV protease inhibitors: antiretroviral agents with anti-inflammatory, anti-angiogenic and anti-tumour activity. J. Antimicrob. Chemother. 51:207-211.
11. Mukwaya, G., T. R. MacGregor, D. Hoelscher, T. Heming, D. Legg, K. Kavanaugh, P. Johnson, J. P. Sabo, and S. McCallister. 2005. Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob. Agents Chemother. 49:4903-4910.
12. Poppe, S. M., D. E. Slade, K. T. Chong, R. R. Hinshaw, P. J. Pagano, M. Markowitz, D. D. Ho, H. Mo, R. R. Gorman III, T. J. Dueweke, S. Thaisrivongs, and W. G. Tarpley. 1997. Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob. Agents Chemother. 41:1058-1063.
13. Roszko, P. J., K. Curry, B. Brazina, A. Cohen, E. L. Turkie, J. P. Sabo, T. R. MacGregor, and S. McCallister. 2003. Standard doses of efavirenz (EFV), zidovudine (ZDV), tenofovir (TDF), and didanosine (ddI) may be given with tipranavir/ritonavir (TPV/r). Antivir. Ther. 8:S428.
14. Sabo, J. P., P. J. Piliero, A. Lawton, T. R. MacGregor, and J. Leith. 2006. A comparison of steady-state trough plasma ritonavir concentrations for HIV+ patients receiving an optimized background regimen and ritonavir-boosted tipranavir (TPV/r), lopinavir (LPV/r), saquinavir (SQV/r) or amprenavir (APV/r), poster 43. In Proceedings of the 7th International Workshop on Clinical Pharmacology of HIV Therapy (Lisbon). Virology Education, Utrecht, The Netherlands.
15. Thaisrivongs, S., and J. W. Strohbach. 1999. Structure-based discovery of tipranavir disodium (PNU-140690E): a potent, orally bioavailable, nonpeptidic HIV protease inhibitor. Biopolymers 51:51-58.
16. Turner, S. R., J. W. Strohbach, R. A. Tommasi, P. A. Aristoff, P. D. Johnson, H. I. Skulnick, L. A. Dolak, E. P. Seost, P. K. Tomich, M. J. Bohanon, M. M. Horng, J. C. Lynn, K. T. Chong, R. R. Hinshaw, K. D. Watenpaugh, M. N. Janakiraman, and S. Thaisrivongs. 1998. Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J. Med. Chem. 41:3467-3476.