Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects

Drug Metabolism and Disposition

Volumn 37, Issue 4, 2009, Pages 809-820

  Vermeir, Marc ^a   Lachau Durand, Sophie ^b   Mannens, Geert ^a   Cuyckens, Filip ^a   Van Hoof, Bart ^a   Raoof, Araz ^b  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b TIBOTEC BVBA   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANILINE; CARBAMIC ACID; DARUNAVIR; RITONAVIR;

ADULT; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG EXCRETION; DRUG METABOLISM; FECES ANALYSIS; GLUCURONIDATION; HUMAN; HYDROLYSIS; HYDROXYLATION; KIDNEY CLEARANCE; MALE; METABOLITE; PRIORITY JOURNAL; RADIOACTIVITY; UNSPECIFIED SIDE EFFECT; URINALYSIS;

ADULT; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; FECES; HIV PROTEASE INHIBITORS; HUMANS; MALE; MIDDLE AGED; REFERENCE VALUES; RITONAVIR; SULFONAMIDES; TANDEM MASS SPECTROMETRY;

HUMAN IMMUNODEFICIENCY VIRUS;

EID: 63849123835     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.024109     Document Type: Article

References (16)

1. Bu HZ, 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.
2. Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wohrmann A, Katlama C, Wilkin T, Haubrich R, et al. (2007) Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet 369:1169-1178.
3. Cooper CL, van Heeswijk RP, Gallicano K, and Cameron DW (2003) A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis 36:1585-1592.
4. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, and de Bethune MP (2005) TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 49:2314-2321.
5. Decker CJ, Laitinen LM, Bridson GW, Raybuck SA, Tung RD, and Chaturvedi PR (1998) Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions. J Pharm Sci 87:803-807.
6. 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.
7. King NM, Prabu-Jeyabalan M, Nalivaika EA, Wigerinck P, de Béthune MP, and Schiffer CA (2004) Structural and thermodynamic basis for the binding of TMC114, a next-generation Human Immunodeficiency virus type 1 protease inhibitor. J Virol 78:12012-12021.
8. Koh Y, Matsumi S, Das D, Amano M, Davis DA, Li J, Leschenko S, Baldridge A, Shioda T, Yarchoan R, et al. (2007) Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization J Biol Chem 282:28709-28720.
9. Lachau-Durand S, Annaert P, Steemans K, Willems B, Mannens G, Raoof A, and Meuldermans W (2006) Transport characteristics of the HIV protease inhibitor darunavir (TMC114) in Caco-2 monolayers. Proceedings of the Annual Meeting of the American Association of Pharmaceutical Sciences; 2006 Oct 29-Nov 2; San Antonio, TX. American Association of Pharmaceutical Sciences, Arlington, VA.
10. Lachau-Durand S, Raoof A, Willems B, Mamidi R, and Meuldermans W (2005) The effect of ritonavir on the pharmacokinetics of TMC114 (darunavir) in several preclinical species. 2005European International Society for the Study of Xenobiotics Meeting; 2005 Jun 12-17; Nice, France. The International Society for the Study of Xenobiotics, Washington, D.C.
11. Mamidi RNVS, Mannens GSJ, Hendrickx J, Vermeir M, Annaert P, Weygers A, Van Looveren C, Lachau-Durand S, Raoof A, and Meuldermans W (2005) Identification of cytochrome P450 (CYP450) enzymes responsible for the metabolism of TMC114, a new protease inhibitor, in human liver microsomes (HLMs). Proceedings of the Annual Meeting of the American Association of Pharmaceutical Sciences; 2006 Nov 6-10; Nashville, TN. American Association of Pharmaceutical Sciences, Arlington, VA.
12. McRae MP, Lowe CM, Tian X, Bourdet DL, Ho RH, Leake BF, Kim RB, Brouwer KL, and Kashuba AD (2006) Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J Pharmacol Exp Ther 318:1068-1075.
13. 14C]-amprenavir, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, administered as a single oral dose to healthy male subjects. J Clin Pharmacol 41:386-396.
14. Vermeir M, Hendrickx J, Van Houdt J, Van Looveren C, Bockx M, Weygers A, Steemans K, Mannens G, Lachau-Durand S, Raoof A, et al. (2006) An interspecies comparison of the in vitro metabolism of the anti-HIV compound TMC114. Proceedings of the 16th International Symposium on Microsomes and Drug Oxidations (MDO); 2006 Sept 3-7; Budapest, Hungary. Institute of Bioorganic Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
15. Wire MB, Shelton MJ, and Studenberg S (2006) Fosamprenavir: clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet 45:137-168.
16. Zeldin RK and Petruschke RA (2004) Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients. J Antimicrob Chemother 53:4-9.