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DDMODEL00000124: Madrasi_2014_HIV_tenofovir

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Linking the population pharmacokinetics of tenofovir and its metabolites with its cellular uptake and metabolism
PharmML (0.6.1)
  • Linking the population pharmacokinetics of tenofovir and its metabolites with its cellular uptake and metabolism.
  • Madrasi K, Burns RN, Hendrix CW, Fossler MJ, Chaturvedula A
  • CPT: pharmacometrics & systems pharmacology, 1/2014, Volume 3, pages: e147
  • Department of Pharmacy Practice, Mercer University, Atlanta, Georgia, USA. Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia, USA. Division of Clinical Pharmacology, John Hopkins University, Baltimore, Maryland, USA. Clinical P
  • 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 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.
Paolo Magni
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  • Model owner: Paolo Magni
  • Submitted: Dec 13, 2015 10:16:56 AM
  • Last Modified: Oct 10, 2016 8:18:55 PM
Revisions
  • Version: 6 public model Download this version
    • Submitted on: Oct 10, 2016 8:18:55 PM
    • Submitted by: Paolo Magni
    • With comment: Update MDL syntax to the version 1.0 and R script to SEE version 2.0.0. Code automatically generated for NONMEM and MONOLIX
  • Version: 5 public model Download this version
    • Submitted on: Jul 16, 2016 5:07:39 PM
    • Submitted by: Paolo Magni
    • With comment: Updated model annotations.
  • Version: 2 public model Download this version
    • Submitted on: Dec 13, 2015 10:16:56 AM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
 
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