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

Abstract

Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), 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), *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 to the wild‐type subjects of CYP2D6 *1/*1, the plasma peak concentration (Cmax) and area under the curve (AUCinf) of dapoxetine in *10/*10 and *10/*41 were notably increased (p ≤ 0.05). Significant differences were observed among the dapoxetine activity score groups in Cmax, AUC, V/F and CL/F (p ≤ 0.05). The AUCinf increased significantly (154% and 89.73%, p ≤ 0.05), and the Cmax increased significantly (73.45% and 42.67%, p ≤ 0.05) when comparing CYP2D6 *10/*41 subjects to *1/*1 and *1/*10 subjects. The obtained results indicated that CYP2D6 *10 and *41 polymorphisms have significant effects on the pharmacokinetic properties of dapoxetine.This article is protected by copyright. All rights reserved