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The Pharmacokinetics of Saquinavir: A Markov Chain Monte Carlo Population Analysis

  • David J. Lunn
  • Leon Aarons
Article

Abstract

Saquinavir is an HIV proteinase inhibitor marketed as a treatment for HIV infection. The drug has potent (Ki ∼ 0.1 nM) antiviral activity and acts by inhibiting the processing of gag and gagpol polyproteins, thus blocking the maturation of replicated viral particles. By assuming standard two-compartment disposition kinetics in combination with a variety of absorption processes we have identified two structural models that perform well with respect to describing the pharmacokinetic behavior of saquinavir when administered to healthy human volunteers from various Phase I studies. These structural models have been implemented for population analysis of these Phase I data via the Bayesian Markov chain Monte Carlo approach. We conclude that saquinavir exhibits complex and highly variable behavior, but can be modeled adequately using a two-compartment zero-order absorption model. There is also an indication that saquinavir kinetics may be time-dependent.

Markov chain Monte Carlo Gibbs sampler population analysis hierarchical models saquinavir 

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Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • David J. Lunn
    • 1
  • Leon Aarons
    • 2
  1. 1.Department of Epidemiology and Public HealthImperial College School of Medicine atLondonUnited Kingdom
  2. 2.University of ManchesterManchesterUnited Kingdom

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