A Population Pharmacokinetic Approach to Understand the Effect of Efavirenz on CYP3A Activity in Healthy Volunteers Using Midazolam as a Probe.

ABSTRACT: Efavirenz induces and inhibits multiple drug-metabolizing enzymes, contributing to significant drug-drug interactions. This study quantified the impact of multiple doses of efavirenz on CYP3A activity via midazolam metabolism using a population pharmacokinetic approach. Healthy volunteers received 1 mg midazolam orally in two sessions: first with a single 600 mg efavirenz dose and then after chronic efavirenz dosing (600 mg/day for 17 days). Midazolam and 1'-hydroxymidazolam were quantified via LC-MS/MS, and CYP2B6, CYP3A4, and CYP3A5 genotypes were assessed using TaqMan assays. Seventy-two volunteers (n = 72) completed sampling after the initial dose, and 58 completed both occasions. Non-linear mixed effects modeling was performed using the stochastic approximation expectation maximizatio

SUBMITTER: Collins KS 

PROVIDER: S-EPMC12706424 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature