Dapoxetine 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.
Keywords: CYP2D6 *10; CYP2D6 *41; activity score; dapoxetine; pharmacokinetics; premature ejaculation.
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