Linking the population pharmacokinetics of tenofovir and its metabolites with its cellular uptake and metabolism.

ABSTRACT: Empirical pharmacokinetic models are used to explain the pharmacokinetics of the antiviral drug tenofovir (TFV) and its metabolite TFV diphosphate (TFV-DP) in peripheral blood mononuclear cells. These empirical models lack the ability to explain differences between the disposition of TFV-DP in HIV-infected patients vs. healthy individuals. Such differences may lie in the mechanisms of TFV transport and phosphorylation. Therefore, we developed an exploratory model based on mechanistic mass transport principles and enzyme kinetics to examine the uptake and phosphorylation kinetics of TFV. TFV-DP median Cmax from the model was 38.5 fmol/10(6) cells, which is bracketed by two reported healthy volunteer studies (38 and 51 fmol/10(6) cells). The model presented provides a foundation for explorat

SUBMITTER: Madrasi K 

PROVIDER: S-EPMC4260001 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature