A population pharmacokinetic meta-analysis of maraviroc in healthy volunteers and asymptomatic HIV-infected subjects

Br J Clin Pharmacol. 2008 Apr;65 Suppl 1(Suppl 1):76-85. doi: 10.1111/j.1365-2125.2008.03139.x.


Aims: To develop a population pharmacokinetic model for maraviroc, a noncompetitive CCR5 antagonist, after oral administration of tablets to healthy volunteers and asymptomatic HIV-infected subjects and to quantify the inherent variability and influence of covariates on the parameters of the model.

Methods: Rich pharmacokinetic data available from 15 studies in healthy volunteers (n = 365) and two studies in asymptomatic HIV-infected subjects (n = 48) were analysed using NONMEM. Maraviroc was administered as single or multiple oral tablet doses under fasted and fed conditions. Doses ranged from 100 to 1800 mg day(-1).

Results: A two-compartment model parameterized to separate out absorption and clearance components on bioavailability was used. Absorption was described by a lagged first-order process. A sigmoid E(max) model described the effect of dose on absorption. A visual predictive check and nonparametric bootstrap evaluation confirmed that the model was a good description of the data. Typical CL, V(c) and V(p) values for a 30-year-old non-Asian are 51.5 l h(-1), 132 l and 277 l, respectively.

Conclusions: For the typical non-Asian subject, fasted bioavailability increased asymptotically with dose from 24% at 100 mg to 33% at 600 mg. A high-fat meal taken with maraviroc reduced exposure by 43% for a 100-mg dose to approximately 25% at doses of 600 mg. The typical Asian subject had a 26.5% higher AUC than the typical non-Asian subject irrespective of dose, a difference not considered to be clinically relevant. None of the other covariates tested had any clinically relevant effects on exposure.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • CCR5 Receptor Antagonists*
  • Computer Simulation
  • Cyclohexanes / pharmacokinetics*
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • Models, Biological
  • Models, Statistical
  • Randomized Controlled Trials as Topic
  • Triazoles / pharmacokinetics*


  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Triazoles
  • Maraviroc