A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention.

ABSTRACT: A priori use of mathematical modeling and simulation to predict outcomes from incomplete adherence or reduced frequency dosing strategies may mitigate the risk of clinical trial failure with HIV pre-exposure prophylaxis regimens. We developed a semi-physiologic population pharmacokinetic model for two antiretrovirals and their active intracellular metabolites in three mucosal tissues using pharmacokinetic data from a phase I, dose-ranging study. Healthy female volunteers were given a single oral dose of tenofovir disoproxil fumarate (150, 300, or 600 mg) or emtricitabine (100, 200, or 400 mg). Simultaneous co-modeling of all data was performed on a Linux cluster. A 16 compartment, bolus input, linear kinetic model best described the data, containing 986 observations in 23 individuals acros

SUBMITTER: Leung E 

PROVIDER: S-EPMC10725258 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature