Miconazole oral gel increases exposure to oral oxycodone by inhibition of CYP2D6 and CYP3A4.
Author(s): Gronlund J, Saari TI, Hagelberg N, Neuvonen PJ, Olkkola KT, Laine K
Affiliation(s): Department of Anesthesiology, Intensive Care, Emergency Care, and Pain Medicine, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland. firstname.lastname@example.org
Publication date & source: 2011-03, Antimicrob Agents Chemother., 55(3):1063-7. Epub 2010 Dec 20.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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-infinity); 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.