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

K. Madrasi, R. N. Burns, Craig Hendrix, M. J. Fossler, A. Chaturvedula

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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/106 cells, which is bracketed by two reported healthy volunteer studies (38 and 51 fmol/106 cells). The model presented provides a foundation for exploration of TFV uptake and phosphorylation kinetics for various routes of TFV administration and can be updated as more is known on actual mechanisms of cellular transport of TFV.

Original languageEnglish (US)
Article numbere147
JournalCPT: Pharmacometrics and Systems Pharmacology
Issue number11
Publication statusPublished - Jan 1 2014


ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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