Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers

Br J Clin Pharmacol. 2008 Apr;65 Suppl 1(Suppl 1):19-26. doi: 10.1111/j.1365-2125.2008.03132.x.


Aims: To assess the effect of maraviroc on the pharmacokinetics of midazolam, a sensitive probe CYP3A4 substrate; lamivudine/zidovudine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs); and ethinyloestradiol/levonorgestrel, a combination oral contraceptive.

Methods: Three randomized, double-blind, placebo-controlled studies were conducted in healthy subjects to assess the effect of maraviroc on pharmacokinetics of other drugs. Two, two-period crossover studies were conducted to assess (i) the effect of steady-state maraviroc (300 mg b.i.d.) on pharmacokinetics of midazolam; and (ii) the effect of steady-state maraviroc (300 mg b.i.d.) on the pharmacokinetics of lamivudine/zidovudine. A third two-way crossover study was conducted to evaluate the effect of steady-state maraviroc (100 mg b.i.d.) on the pharmacokinetics of 30 microg ethinyloestradiol/150 microg levonorgestrel (Microgynon).

Results: The geometric mean ratios for C(max) and AUC for each of the compounds tested in the presence and absence of maraviroc were between 92% and 121%. There were no notable differences in T(max), t(1/2) or CL(R) (where measured) for any of the compounds.

Conclusions: Maraviroc had no clinically relevant effects on the pharmacokinetics of the CYP3A4 substrate midazolam, the NRTIs zidovudine/lamivudine, or the oral contraceptive steroids ethinyloestradiol and levonorgestrel.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Anxiety Agents / blood
  • Anti-Anxiety Agents / pharmacokinetics*
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • CCR5 Receptor Antagonists*
  • Contraceptives, Oral / blood
  • Contraceptives, Oral / pharmacokinetics*
  • Cyclohexanes / pharmacology*
  • Double-Blind Method
  • Drug Interactions
  • Drug Therapy, Combination
  • Ethinyl Estradiol / blood
  • Ethinyl Estradiol / pharmacokinetics
  • Female
  • HIV Infections / drug therapy
  • Humans
  • Lamivudine / blood
  • Lamivudine / pharmacokinetics
  • Levonorgestrel / blood
  • Levonorgestrel / pharmacokinetics
  • Male
  • Maraviroc
  • Midazolam / blood
  • Midazolam / pharmacokinetics
  • Middle Aged
  • Statistics as Topic
  • Triazoles / pharmacology*
  • Zidovudine / blood
  • Zidovudine / pharmacokinetics


  • Anti-Anxiety Agents
  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Contraceptives, Oral
  • Cyclohexanes
  • Triazoles
  • Lamivudine
  • Ethinyl Estradiol
  • Zidovudine
  • Levonorgestrel
  • Maraviroc
  • Midazolam