Effects of CYP2D6 *10 and *41 Variants in Healthy Chinese Men on the Pharmacokinetics of Dapoxetine

Abstract

AbstractDapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and flavin‐containing monooxygenase 1. The purpose of the study was to evaluate the effect of CYP2D6 polymorphism on the pharmacokinetics of dapoxetine in healthy Chinese men. Thirty‐nine subjects who received a single oral dose of 30 mg dapoxetine hydrochloride were classified based on their CYP2D6 genotype: *1/*1 (n = 9), *1/*41 (n = 1), *1/*10 (n = 12), *10/*41 (n = 3), or *10/*10 (n = 14). The difference in pharmacokinetic parameters between different genotype groups was analyzed and then scored according to the activity score system. Compared with the wild‐type subjects of CYP2D6 *1/*1, the peak plasma concentration (Cmax) and the area under the plasma drug concentration‐time curve (AUCinf) of dapoxetine in the *10/*10 and *10/*41 groups were notably increased (P ≤ .05). Significant differences in Cmax, AUC, volume of distribution/bioavailability (V/F) and clearance/bioavailability (CL/F) were observed among dapoxetine activity score groups (P ≤ .05). The AUCinf was increased significantly (154% and 89.73%, P ≤ .05) and the Cmax was increased significantly (73.45% and 42.67%, P ≤ .05) in CYP2D6 *10/*41 subjects, compared with CYP2D6 *1/*1 and *1/*10 subjects. The results obtained indicated that CYP2D6 *10 and *41 polymorphisms have significant effects on the pharmacokinetic properties of dapoxetine.