title: Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers.
abstract: OBJECTIVE
  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.
authors.affiliation: Pfizer Global R&D, Sandwich, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Abel
authors.forename: Deborah
authors.initials: D
authors.lastname: Russell
authors.forename: Lyndsey A
authors.initials: LA
authors.lastname: Whitlock
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Ridgway
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Muirhead
mesh_terms: D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics*; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics*; D065100:CCR5 Receptor Antagonists; D003276:Contraceptives, Oral / Q000097:blood / Q000493:pharmacokinetics*; D003510:Cyclohexanes / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics; D016912:Levonorgestrel / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D000077592:Maraviroc; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D013223:Statistics as Topic; D014230:Triazoles / Q000494:pharmacology*; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D014151:Anti-Anxiety Agents; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003276:Contraceptives, Oral; D003510:Cyclohexanes; D014230:Triazoles; D019259:Lamivudine; D004997:Ethinyl Estradiol; D015215:Zidovudine; D016912:Levonorgestrel; D000077592:Maraviroc; D008874:Midazolam