Content area
Abstract
Objective Paroxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine. Methods Two 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing. Results Compared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (Cmax) of paroxetine, by 1.9-fold (6.4+/-2.4 versus 12.1+/-2.9 ng/ml, p<0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0-48)] of paroxetine by 2.5-fold (127+/-67 vs 318+/-102 ng/ml, p<0.001). Elimination half-life differed significantly (15.3+/-2.4 vs 22.7+/-8.8 h, p<0.05), although the magnitude of alteration (1.4-fold) was smaller than Cmax or AUC. Conclusion The present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state. [PUBLICATION ABSTRACT]