Our aim was to assess the effect of miconazole oral gel on the pharmacokinetics of oral oxycodone. In an open crossover study with two phases, 12 healthy volunteers took a single oral dose of 10 mg of immediate-release oxycodone with or without thrice-daily 85-mg miconazole oral gel treatment. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h. Pharmacological effects of oxycodone were recorded for 12 h. Pharmacokinetic parameters were compared by use of the geometric mean ratios (GMRs) and their 90% confidence interval (CIs). Pretreatment with miconazole oral gel caused a strong inhibition of the CYP2D6-dependent metabolism and moderate inhibition of the CYP3A4-dependent metabolism of oxycodone. The mean area under the concentration-time curve (AUC) from time zero to infinity (AUC 0-ؕ ; GMR, 1.63; 90% CI, 1.48 to 1.79) and the peak concentration of oxycodone (GMR, 1.31; 90% CI, 1.19 to 1.44) were increased. The AUC of the CYP2D6-dependent metabolite oxymorphone was greatly decreased (GMR, 0.17; 90% CI, 0.09 to 0.31) by miconazole gel, whereas that of the CYP3A4-dependent metabolite noroxycodone was increased (GMR, 1.30; 90% CI, 1.15 to 1.47) by miconazole gel. Differences in the pharmacological response to oxycodone between phases were insignificant. Miconazole oral gel increases the exposure to oral oxycodone, but the clinical relevance of the interaction is moderate. Miconazole oral gel produces a rather strong inhibitory effect on CYP2D6, which deserves further study.Miconazole is a broad-spectrum azole antifungal agent. Due to its limited oral bioavailability and a high risk of drug interactions, the systemic use of miconazole is rare. However, miconazole is commonly used as a topical preparation (16,21). In vitro studies have shown miconazole to be a strong inhibitor of many drug-metabolizing cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) (19,20). Compared with systemic use, the risk for drug interactions is markedly reduced when miconazole is used topically. However, there are many case reports and one controlled study indicating that clinically relevant CYP-mediated drug interactions are also possible when miconazole is used as a topical preparation, especially as an oral gel (6,11,23).Oxycodone is an opioid analgesic which is increasingly used in inpatient and outpatient care (7, 10). The metabolism of oxycodone is catalyzed by CYP2D6 and CYP3A4 enzymes (14). The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a small part of oxycodone undergoes 3-O-demethylation to oxymorphone by CYP2D6. Further oxidation of these metabolites via CYP2D6 and CYP3A4, respectively, yields noroxymorphone (13). Although the metabolites show variable -opioid receptor activity, it seems that the parent drug is responsible for the central opioid effects (13).Recent studies have shown that concomitantly administered drugs which inhibit CYP enzymes may significantly alter the pharmacokinetics of oxyc...