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

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 μg ethinyloestradiol/150 μg levonorgestrel (Microgynon®). RESULTS The geometric mean ratios for Cmax 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 Tmax, t1/2 or CLR (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.