Oral voriconazole and miconazole oral gel produce comparable effects on the pharmacokinetics and pharmacodynamics of etoricoxib

Purpose The effect of topical miconazole oral gel and systemic oral voriconazole on the pharmacokinetics of oral etoricoxib was studied in 12 healthy volunteers. Methods Plasma concentrations of etoricoxib, miconazole, voriconazole, and thromboxane B-2 generation were followed after ingestion of 60 mg etoricoxib without pretreatment, after topical administration of miconazole oral gel (85 mg x 3, 3 days), or after oral voriconazole (400 mg x 2, 1st day, 200 mg x 2, 2nd day). Results Etoricoxib area under the plasma concentration time curve (AUC(0-infinity)) and maximum plasma concentration (C-max) geometric mean ratios (GMR) with/without miconazole were 1.69 {90% confidence interval (CI); 1.46-1.92} and 1.12 (90% CI; 0.99-1.25), respectively, and corresponding GMRs with/without voriconazole were 1.49 (90% CI; 1.37-1.61) and 1.19 (90% CI; 1.08-1.31), respectively. Conclusions Miconazole oral gel and oral voriconazole produced comparable increase in the exposure to etoricoxib, presumably via CYP3A inhibition.