AIMS: Voriconazole is a triazole antifungal agent with potent fungicidal activity against Aspergillus species. Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. This aim of this study was to investigate the effect of multiple-dose voriconazole on the steady-state pharmacokinetics of digoxin in healthy male volunteers. METHODS: This was a double-blind, randomized, placebo-controlled, parallel-group study. All subjects received daily administration of oral digoxin for a total of 22 days (0.5 mg twice daily on day 1, 0.25 mg twice daily on day 2 and 0.25 mg once daily on days 3-22). In addition, on days 11-22 the subjects were randomized to receive either voriconazole (200 mg twice daily) or matching placebo. RESULTS: Concomitant administration with voriconazole did not significantly alter the Cmax, AUCtau, tmax or CLR of digoxin at steady state. The ratios between groups for Cmax and AUCtau at day 22, corrected for baseline (day 10) were 109.8%[90% confidence interval (CI) 97.1, 124.1] and 100.5% (90% CI 91.4, 110.5), respectively. In addition, group mean Cmin values were similar in both treatment groups throughout the study. There were no significant differences between treatments with respect to the incidence of adverse events, all of which were classified as mild and transient in nature. CONCLUSIONS: The steady-state pharmacokinetics of digoxin are not affected in a clinically relevant manner by the concomitant administration of voriconazole.
RCT Entities:
AIMS: Voriconazole is a triazole antifungal agent with potent fungicidal activity against Aspergillus species. Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. This aim of this study was to investigate the effect of multiple-dose voriconazole on the steady-state pharmacokinetics of digoxin in healthy male volunteers. METHODS: This was a double-blind, randomized, placebo-controlled, parallel-group study. All subjects received daily administration of oral digoxin for a total of 22 days (0.5 mg twice daily on day 1, 0.25 mg twice daily on day 2 and 0.25 mg once daily on days 3-22). In addition, on days 11-22 the subjects were randomized to receive either voriconazole (200 mg twice daily) or matching placebo. RESULTS: Concomitant administration with voriconazole did not significantly alter the Cmax, AUCtau, tmax or CLR of digoxin at steady state. The ratios between groups for Cmax and AUCtau at day 22, corrected for baseline (day 10) were 109.8%[90% confidence interval (CI) 97.1, 124.1] and 100.5% (90% CI 91.4, 110.5), respectively. In addition, group mean Cmin values were similar in both treatment groups throughout the study. There were no significant differences between treatments with respect to the incidence of adverse events, all of which were classified as mild and transient in nature. CONCLUSIONS: The steady-state pharmacokinetics of digoxin are not affected in a clinically relevant manner by the concomitant administration of voriconazole.
Authors: R B Kim; C Wandel; B Leake; M Cvetkovic; M F Fromm; P J Dempsey; M M Roden; F Belas; A K Chaudhary; D M Roden; A J Wood; G R Wilkinson Journal: Pharm Res Date: 1999-03 Impact factor: 4.200
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: Nina Isoherranen; Justin D Lutz; Sophie P Chung; Houda Hachad; Rene H Levy; Isabelle Ragueneau-Majlessi Journal: Chem Res Toxicol Date: 2012-09-27 Impact factor: 3.739
Authors: Takao Yamazaki; Amit Desai; Ronald Goldwater; David Han; Kenneth C Lasseter; Corrie Howieson; Shahzad Akhtar; Donna Kowalski; Christopher Lademacher; Diane Rammelsberg; Robert Townsend Journal: Clin Pharmacol Drug Dev Date: 2016-07-15