Cytochrome P450 3A5 plays a prominent role in the oxidative metabolism of the anti-human immunodeficiency virus drug maraviroc.

ABSTRACT: Maraviroc is an anti-human immunodeficiency virus drug that acts by blocking viral entry into target cells. With use of ultra-performance liquid chromatography-mass spectrometry several monooxygenated, dioxygenated, and glucuronidated metabolites of maraviroc were identified both in vitro and in vivo. Characterization of the enzymes involved in the production of these metabolites determined that cytochrome P450 3A5 was the principal enzyme responsible for the formation of an abundant metabolite of maraviroc that resulted from oxygenation of the dichlorocyclohexane ring. For the formation of this metabolite, the V(max) values for CYP3A4 and CYP3A5 were 0.04 and 0.93 pmol · min⁻¹ · pmol P450⁻¹, and the K(m) values were 11.1 and 48.9 μM, respectively. Furthermore, human liver microsomes isola

SUBMITTER: Lu Y 

PROVIDER: S-EPMC3500548 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature