Metabolism and disposition of the HIV-1 protease inhibitor ritonavir (ABT-538) in rats, dogs, and humans

Drug Metabolism and Disposition

Volumn 25, Issue 4, 1997, Pages 489-501

  Denissen, Jon F ^a   Grabowski, Brian A ^b   Johnson, Marianne K ^b   Buko, Alex M ^b   Kempf, Dale J ^b   Thomas, Samuel B ^b   Surber, Bruce W ^b  

^a ABBOTT LABORATORIES   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; PROTEINASE INHIBITOR; RITONAVIR;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DOG; DRUG BILE LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TISSUE LEVEL; DRUG URINE LEVEL; FEMALE; HUMAN; HUMAN EXPERIMENT; INTRADUODENAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RADIOACTIVITY; RAT; SPECIES DIFFERENCE;

ADULT; ANIMALS; BILE; BLOOD PROTEINS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOGS; FECES; FEMALE; HIV PROTEASE INHIBITORS; HUMANS; MALE; MASS SPECTROMETRY; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; RITONAVIR; TISSUE DISTRIBUTION;

EID: 0030963109     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (18)

1. D. J. Kempf, K. C. Marsh, J. F. Denissen, E. McDonald, S. Vasavanonda, C. A. Flentge, B. E. Green, L. Fino, C. H. Park, X.-P. Kong, N. E. Wideburg, A. Saldivar, L. Ruiz, W. M. Kati, H. L. Sham, T. Robins, K. D. Stewart, A. Hsu, J. J. Plattner, J. M. Leonard, and D. W. Norbeck: ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc. Natl. Acad. Sci. USA 92, 2484-2488 (1995).
2. D. J. Kempf: Progress in the discovery of orally bioavailable inhibitors of HIV protease. Perspec. Drug Discov. Design 2, 427-436 (1994).
3. D. D. Ho, A. U. Neumann, A. S. Perelson, W. Chen, J. M. Leonard, and M. Markowitz: Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature (Lond.) 373, 123-126 (1995).
4. X. Wei, S. K. Ghosh, M. E. Taylor, V. A. Johnson, E. A. Emini, P. Deutsch, J. D. Lifson, S. Bonhoeffer, M. A. Nowak, B. H. Hahn, M. S. Saag, and G. M. Shaw: Viral dynamics in human immunodeficiency virus type 1 infection. Nature (Lond.) 373, 117-122 (1995).
5. S. A. Danner, A. Carr, J. M. Leonard, L. M. Lehman, F. Gudiol, J. Gonzales, A. Raventos, R. Rubio, E. Bouza, V. Pintado, A. Gil Aguado, J. Garcia de Lomas, R. Delgado, J. C. C. Borleffs, A. Hsu, J. M. Valdes, C. A. B. Boucher, and D. A. Cooper. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. N. Engl. J. Med. 333, 1528-1533 (1995).
6. G. Pantaleo, C. Graziosi, and A. S. Fauci. The immunopathogenesis of human immunodeficiency virus infection. N. Engl. J. Med. 328, 327-334 (1993).
7. G. N. Kumar, A. D. Rodrigues, A. M. Buko, and J. F. Denissen: Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J. Pharmacol. Exp. Ther. 277, 423-431 (1996).
8. D. J. Kempf, unpublished results.
9. X.-J. Zhang and P. E. Thomas: Erythromycin as a specific substrate for cytochrome P4503A isozymes and identification of a high-affinity erythromycin N-demethylase in adult female rats. Drug Metab. Dispos. 24, 23-27 (1996).
10. M. J. Waskiewicz, S. Choudhuri, S. M. Vanderbeck, X.-J. Zhang and P. E. Thomas: Induction of "male-specific" cytochrome P450 isozymes in female rats by oxandrolone. Drug Metab. Dispos. 23, 1291-1296 (1995).
11. T. J. Jaworski, E. M. Hawes, J. W. Hubbard, G. McKay and K. K. Midha. The metabolites of chlorpromazine N-oxide in rat bile. Xenobiotica 21, 1451-1459 (1991).
12. P. Jenner, J. W. Gorrod and A. H. Beckett. The absorption of nicotine-1′-N-oxide and its reduction in the gastrointestinal tract in man. Xenobiotica 3, 341-349 (1973).
13. R. M. Dajani, J. W. Gorrod and A. H. Beckett. Reduction in vivo of (-)-nicotine-1′-N-oxide by germ-free and conventional rats. Biochem. Pharmacol. 24, 648-650 (1975).
14. S. C. Lee and A. G. Renwick: Sulfoxide reduction by rat intestinal flora and by Escherichia coli in vitro. Biochem. Pharmacol. 49, 1567-1576 (1995).
15. U. Wetterich, H. Spahn-Langguth, E. Mutschler, B. Terhaag, W. Rosch and P. Langguth: Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration-and dose-dependent absorption in vitro and in vivo. Pharm. Res. 13, 514-522 (1996).
16. M. Koike, R. Norikura, S. Futaguchi, T. Yamaguchi, K. Sugeno, K. Iwatani, Y. Ikenishi and Y. Nakagawa: N-Hydroxymethyl metabolites of 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative, in dog plasma. Drug Metab. Dispos. 15, 426-428 (1987).
17. A. M. Starret, W. G. Humphreys, M. T. Obermeier and G. C. DiDonato: Characterization of HIV protease inhibitor metabolites by ionspray LC/MS and LC/MS/MS techniques. Forty-second American Society for Mass Spectrometry Conference, Chicago, May 29-June 3, 1994. Abstract TP-26.
18. S. K. Balani, S. M. Pitzenberger, M. S. Schwartz, H. G. Ramjit and W. J. Thompson: Metabolism of L-689,502 by rat liver slices to potent HIV-1 protease inhibitors. Drug Metab. Dispos. 23, 185-189 (1995).