AIMS: 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 Most adverse events were mild and transitory; two subjects were withdrawn due to adverse events.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.
RCT Entities:
AIMS: 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: M Cuenca-Estrella; J L Rodríguez-Tudela; E Mellado; J V Martínez-Suárez; A Monzón Journal: J Antimicrob Chemother Date: 1998-10 Impact factor: 5.790
Authors: Brad Moriyama; Jason Elinoff; Robert L Danner; Juan Gea-Banacloche; Gennethel Pennick; Michael G Rinaldi; Thomas J Walsh Journal: Antimicrob Agents Chemother Date: 2009-01-26 Impact factor: 5.191
Authors: Peter G Pappas; Carol A Kauffman; David R Andes; Cornelius J Clancy; Kieren A Marr; Luis Ostrosky-Zeichner; Annette C Reboli; Mindy G Schuster; Jose A Vazquez; Thomas J Walsh; Theoklis E Zaoutis; Jack D Sobel Journal: Clin Infect Dis Date: 2015-12-16 Impact factor: 9.079
Authors: Xia Li; Sebastian Frechen; Daniel Moj; Thorsten Lehr; Max Taubert; Chih-Hsuan Hsin; Gerd Mikus; Pertti J Neuvonen; Klaus T Olkkola; Teijo I Saari; Uwe Fuhr Journal: Clin Pharmacokinet Date: 2020-06 Impact factor: 6.447
Authors: Laura L Kovanda; Francisco M Marty; Johan Maertens; Amit V Desai; Christopher Lademacher; Marc Engelhardt; Qiaoyang Lu; William W Hope Journal: Antimicrob Agents Chemother Date: 2017-05-24 Impact factor: 5.191