Effect of intrinsic and extrinsic factors on the pharmacokinetics of TMC278 in antiretroviral-naïve, HIV-1-infected patients in ECHO and THRIVE

Methods A total of 1368 patients (24% female) were randomised (1:1) to either TMC278 25 mg q.d. or EFV 600 mg q.d., in combination with TDF/FTC (ECHO) or a choice of either TDF/FTC or AZT/3TC or ABC/3TC (THRIVE). The pharmacokinetics of TMC278 were best described by a two-compartment disposition model in which absorption was characterised by a lag time followed by a sequential zeroand first-order process. Individual values for TMC278 trough plasma concentrations (Ctrough) and area under the plasma concentration-time profile over the dosing interval (AUC24h) were estimated from sparse pharmacokinetic sampling in 679 patients in the TMC278 treatment group (8 samples/48 weeks/patient) using the population pharmacokinetic model. In addition, the potential relationship between selected covariates and the TMC278 apparent oral clearance was evaluated.