Evaluation of capravirine as a CYP3A probe substrate: In vitro and in vivo metabolism of capravirine in rats and dogs

Drug Metabolism and Disposition

Volumn 35, Issue 9, 2007, Pages 1593-1602

  Bu, Hai Zhi ^a   Zhao, Ping ^a,b   Kang, Ping ^a   Pool, William F ^a   Wu, Ellen Y ^a   Shetty, Bhasker V ^a  

^a PFIZER INC   (United States)

^b Sonus Pharmaceuticals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CAPRAVIRINE; CYTOCHROME P450 3A; DRUG METABOLITE; RITONAVIR;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARBOXYLATION; CONTROLLED STUDY; DOG; DRUG ABSORPTION; DRUG ELIMINATION; DRUG METABOLISM; DRUG SCREENING; ENZYME SUBSTRATE; IN VITRO STUDY; IN VIVO STUDY; MALE; MICROSOME; NONHUMAN; OXYGENATION; PRIORITY JOURNAL; RADIOACTIVITY; RAT; SINGLE DRUG DOSE;

ANIMALS; ANTI-HIV AGENTS; ANTIBODIES, BLOCKING; BIOTRANSFORMATION; CHROMATOGRAPHY, LIQUID; CYTOCHROME P-450 CYP3A; DOGS; IMIDAZOLES; MALE; MASS SPECTROMETRY; MICROSOMES, LIVER; RATS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; RITONAVIR; SPECIES SPECIFICITY; SUBSTRATE SPECIFICITY; SULFUR COMPOUNDS;

ANIMALIA; CANIS FAMILIARIS; RATTUS;

EID: 34548098463     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.107.016147     Document Type: Article

References (17)

1. Andrieux C, Membre JM, Cayuela C, and Antoine JM (2002) Metabolic characteristics of the faecal microflora in humans from three age groups. Scand J Gastroenterol 37:792-798.
2. Bu H-Z, Kang P, Zhao P, Pool WF, and Wu EY (2005) A simple sequential incubation method for deconvoluting the complicated sequential metabolism of capravirine in humans. Drug Metab Dispos 33:1438-1445.
3. Bu H-Z, Pool WF, Wu EY, Raber SR, Amantea MA, and Shetty BV (2004) Metabolism and excretion of capravirine, a new non-nucleoside reverse transcriptase inhibitor, alone and in combination with ritonavir in healthy volunteers. Drug Metab Dispos 32:689-698.
4. Bu H-Z, Pool WF, Wu EY, and Shetty BV. (2007) A unique example of drug metabolism: tetra-and penta-oxygenation reactions of capravirine in rats, dogs and humans Drug Metab Lett 1:61-657.
5. Bu H-Z, Zhao P, Kang P, Pool WF, and Wu EY (2006) Identification of enzymes responsible for primary and sequential oxygenation reactions of capravirine in human liver microsomes. Drug Metab Dispos 34:1798-1802.
6. Debri K, Boobis AR, Davies DS, and Edwards RJ (1995) Distribution and induction of CYP3A1 and CYP3A2 in rat liver and extrahepatic tissues. Biochem Pharmacol 50:2047-2056.
7. Doherty MM and Charman WN (2002) The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism? Clin Pharmacokinet 41:235-253.
8. Fraser DJ, Feyereisen R, Harlow GR, and Halpert JR (1997) Isolation, heterologous expression and functional characterization of a novel cytochrome P450 3A enzyme from a canine liver cDNA library. J Pharmacol Exp Ther 283:1425-1432.
9. Fujiwara T, Sato A, el-Farrash M, Miki S, Abe K, Isaka Y, Kodama M, Wu Y, Chen LB, Harada H, et al. (1998) S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1. Antimicrob Agents Chemother 42:1340-1345.
10. Fujiwara T, Sato A, Patick AK, and Potts KE (1999) In vitro antiviral activity and resistance profile of AG1549 (S-1153), a new non-nucleoside inhibitor of HIV-1 reverse transcriptase. Int Antiviral News 7:18-20.
11. Kageyama M, Namiki H, Fukushima H, Terasaka S, Togawa T, Tanaka A, Ito Y, Shibata N, and Takada K (2005) Effect of chronic administration of ritonavir on function of cytochrome P450 3A and P-glycoprotein in rats. Biol Pharm Bull 28:130-137.
12. Lu P, Singh SB, Carr BA, Fang Y, Xiang CD, Rushmore TH, Rodrigues AD, and Shou M (2005) Selective inhibition of dog hepatic CYP2B11 and CYP3A12. J Pharmacol Exp Ther 313: 518-528.
13. Ohkawa T, Goto S, Miki S, Sato A, Kuroda T, Iwatani K, Takeuchi M, and Nakano M (1998) Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes. Xenobiotica 28:877-886.
14. Ren J, Nichols C, Bird LE, Fujiwara T, Sugimoto H, Stuart DI, and Stammers DK (2000) Binding of the second generation non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding. J Biol Chem 275:14316-14320.
15. 14C]L-valinamide, a potent human immunodeficiency virus-1 protease inhibitor, in rats using quantitative wholebody autoradiography. Drug Metab Dispos 30:1164-1169.
16. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, Daily JP, Harmatz JS, and Shader RI (1998) Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol 38:106-111.
17. Wacher VJ, Salphati L, and Benet LZ (1996) Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv Drug Del Rev 20:99-112.