Glucuronidation of the antiretroviral drug efavirenz by UGT2B7 and an in vitro investigation of drug-drug interaction with zidovudine.

ABSTRACT: The non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) is directly conjugated by the UDP-glucuronosyltransferase (UGT) pathway to form EFV-N-glucuronide (EFV-G), but the enzyme(s) involved has not yet been identified. The glucuronidation of EFV was screened with UGT1A and UGT2B enzymes expressed in a heterologous system, and UGT2B7 was shown to be the only reactive enzyme. The apparent K(m) value of UGT2B7 (21 microM) is similar to the value observed for human liver microsomes (24 microM), whereas the variant allozyme UGT2B7*2 (Tyr(268)) displayed similar kinetic parameters. Because 3'-azido-3'-deoxythymidine (AZT), one of the most current nucleotide reverse transcriptase inhibitors prescribed in combination with EFV, is also conjugated by UGT2B7, the potential metabolic intera

SUBMITTER: Belanger AS 

PROVIDER: S-EPMC2729325 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature