Pharmacometric characterization of efavirenz developmental pharmacokinetics and pharmacogenetics in HIV-Infected children

Ahmed Hamed Salem, Courtney V. Fletcher, Richard C. Brundage

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The aim of this analysis was to create a pharmacometric model of efavirenz developmental pharmacokinetics and pharmacogenetics in HIV-infected children. The data consisted of 3,172 plasma concentrations from 96 HIV-1-infected children who participated in the Pediatric AIDS Clinical Trials Group 382 (PACTG382) study. Analyses were performed using NONMEM, and the impacts of body weight, age, race, sex, formulation, liver function, and cytochrome P450 2B6 (CYP2B6)-G516T and multidrugresistance transporter gene (MDR1)-C3435T polymorphisms were assessed. A one-compartment model using weight-based allometry on oral clearance and apparent volume of distribution adequately described the data. A sigmoid maximum-effect (Emax) maturation model demonstrated an increase in oral clearance with age to reach 90% of its mature level by the age of 9 months. The liquid formulation bioavailability relative to the capsule was found to increase with age to reach 90% of its mature value by the age of 8 years. The CYP2B6-G516T polymorphism decreased oral clearance, while the MDR1-C3435T polymorphism demonstrated no effect.

Original languageEnglish (US)
Pages (from-to)136-143
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume58
Issue number1
DOIs
StatePublished - Jan 2014

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