Efavirenz and CYP2C9 Genetic Polymorphisms Reduce CYP2C9 Activity in Healthy Participants.

ABSTRACT: Efavirenz's effects on cytochrome P450 2C9 (CYP2C9) activity have not been formally characterized in vivo. We conducted the first clinical drug-drug interaction (DDI) study to test the effect of chronic efavirenz dosing on CYP2C9 activity, using tolbutamide as a selective probe. Healthy participants received a single oral dose of tolbutamide (250 mg) with a single 600 mg dose of efavirenz (SD) before and after 600 mg daily efavirenz for 17 days (MD). Tolbutamide, efavirenz, and their metabolites were quantified in plasma and urine samples by LC-MS/MS method. Participants were genotyped for CYP2C9*2 and *3 and for CYP2B6*4, *9, and *18. Pharmacokinetic data were valid for 71 and 59 participants for SD- and MD groups, respectively. MD efavirenz caused more than 50% increase in median tolbuta

SUBMITTER: Kim JD 

PROVIDER: S-EPMC12817472 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature