Nonsignificant changes observed for azithromycin on voriconazole pharmacokinetics.
No Clinically Significant Effect of Erythromycin or Azithromycin on the Pharmacokinetics of Voriconazole in Healthy Male Volunteers
^
Study Design
In an open, randomized, parallel-group, single-centre study, 30 healthy male subjects aged 20-41 years received oral voriconazole 200 mg twice daily for 14 days plus either erythromycin (1 g twice daily on days 8-14), azithromycin (500 mg once daily on days 12-14) or placebo (twice daily on days 8-14). Only morning doses were administered on day 14. Plasma concentrations of voriconazole were measured up to 12 h postdose on days 7 and 14, and plasma pharmacokinetic parameters were calculated. Adverse events and standard laboratory test results were recorded before and throughout the study.
Study Results
Comparison of the voriconazole Cmax day 14/day 7 ratio for the voriconazole erythromycin group with that of the voriconazole placebo group yielded a ratio of 107.790 confidence interval (CI) 90.6, 128.0; for the voriconazole azithromycin group, the ratio was 117.5 (90 CI 98.8, 139.7). Comparison of the voriconazole AUCtau day 14/day 7 ratios of the voriconazole erythromycin and voriconazole azithromycin groups with that of the voriconazole placebo group showed ratios of 101.2 (90 CI 89.1, 114.8) and 107.9 (90 CI 95.1, 122.4), respectively. For voriconazole tmax, the differences between the day 14-day 7 calculations for the voriconazole erythromycin or the voriconazole azithromycin groups and that of the voriconazole placebo group were - 0.2 h (90 CI - 0.8, 0.3) and - 0.1 h (90 CI - 0.7, 0.5), respectively. None of these changes was considered clinically relevant. The study drugs were well tolerated by subjects in all groups; the most common study drug-related adverse events were visual disturbances, reported in all groups, and abdominal pain, present in the voriconazole erythromycin group.
Study Conclusions
Coadministration of erythromycin or azithromycin does not affect the steady-state pharmacokinetics of voriconazole in a clinically relevant manner in healthy male subjects.
References
Purkins L. No clinically significant effect of erythromycin or azithromycin on the pharmacokinetics of voriconazole in healthy male volunteers. Br J Clin Pharmacol. 2003; Suppl 1: 30-6.
icon on your home screen.