Trial reportCPT: pharmacometrics & systems pharmacology2025
A Population Pharmacokinetic Approach to Understand the Effect of Efavirenz on CYP3A Activity in Healthy Volunteers Using Midazolam as a Probe.
Trial report in CPT: pharmacometrics & systems pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Efavirenz and CYP2C9 Genetic Polymorphisms Reduce CYP2C9 Activity in Healthy Participants.Clinical and translational science · 2026Article
Corrections and comments
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Authors and funding
7 authors.
Funding
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 maximization estimation method in NONMEM. The base pharmacokinetic model employed was a two-compartment model with first-order absorption and first-order elimination, incorporating proportional error terms for midazolam and 1'-hydroxymidazolam. Covariate analysis utilized a full model approach to assess the impact of CYP3A4 and CYP3A5 genotypes, self-reported sex, and multiple doses of efavirenz as covariates affecting the formation clearance of 1-OH midazolam. CYP3A5 expressors exhibited a 1.27-fold increase in midazolam clearance compared to non-expressors, while CYP3A4 intermediate metabolizers showed a 0.94-fold decrease relative to normal metabolizers. Clearance was also 1.30-fold higher in females compared to males. Multiple doses of efavirenz increased midazolam clearance by 1.92-fold (95% CI 1.65-2.28) after accounting for inter-individual variability caused by other covariates. Furthermore, K
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