title: Histamine H2-receptor antagonists have no clinically significant effect on the steady-state pharmacokinetics of voriconazole.
abstract: OBJECTIVE
  Voriconazole, a new triazole antifungal agent, is metabolized mainly by cytochrome P450s CYP2C19 and CYP2C9, and also by CYP3A4. The aim of this open-label, placebo-controlled, randomized, three-way crossover study was to determine the effects of cimetidine and ranitidine on the steady-state pharmacokinetics of voriconazole.
  
  
  METHODS
  Twelve healthy male subjects received oral voriconazole 200 mg twice daily plus cimetidine 400 mg twice daily, voriconazole 200 mg twice daily plus ranitidine 150 mg twice daily, and voriconazole 200 mg twice daily plus placebo twice daily. Treatment periods were separated by at least 7 days.
  
  
  RESULTS
  When cimetidine was administered with voriconazole, the maximum plasma voriconazole concentration (Cmax) and the area under the plasma concentration-time curve of voriconazole (AUCtau) was increased by 18.3%[90% confidence interval (CI) 6.0, 32.0] and 22.5% (90% CI 13.3, 32.5), respectively. Concomitant ranitidine had no significant effect on voriconazole Cmax or AUCtau. Time of Cmax (tmax) elimination half-life (t 1/2) or terminal phase rate constant (kel) for voriconazole were similar in all three treatment groups. Most adverse events were mild and transitory; two subjects were withdrawn due to adverse events.
  
  
  CONCLUSIONS
  Coadministration of the histamine H2-receptor antagonists cimetidine or ranitidine does not affect the steady-state pharmacokinetics of voriconazole in a clinically relevant manner.
authors: Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK.
authors: Lynn
authors: L
authors: Purkins
authors: Nolan
authors: N
authors: Wood
authors: Diane
authors: D
authors: Kleinermans
authors: Don
authors: D
authors: Nichols
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002927:Cimetidine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011899:Ranitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D006635:Histamine H2 Antagonists; D011743:Pyrimidines; D014230:Triazoles; D002927:Cimetidine; D011899:Ranitidine; D065819:Voriconazole