Model-based estimates of the effects of efavirenz on bedaquiline pharmacokinetics and suggested dose adjustments for patients coinfected with HIV and tuberculosis.

ABSTRACT: Safe, effective concomitant treatment regimens for tuberculosis (TB) and HIV infection are urgently needed. Bedaquiline (BDQ) is a promising new anti-TB drug, and efavirenz (EFV) is a commonly used antiretroviral. Due to EFV's induction of cytochrome P450 3A4, the metabolic enzyme responsible for BDQ biotransformation, the drugs are expected to interact. Based on data from a phase I, single-dose pharmacokinetic study, a nonlinear mixed-effects model characterizing BDQ pharmacokinetics and interaction with multiple-dose EFV was developed. BDQ pharmacokinetics were best described by a 3-compartment disposition model with absorption through a dynamic transit compartment model. Metabolites M2 and M3 were described by 2-compartment models with clearance of BDQ and M2, respectively, as input. Im

SUBMITTER: Svensson EM 

PROVIDER: S-EPMC3716161 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature