Impacts of Cytochrome P450 2D6*10 Allele and a High-Fat Meal on the Pharmacokinetics of Dapoxetine in Healthy Chinese Men: A Single-Dose, Two-Treatment Study.

Abstract

Factors that impact the pharmacokinetics of dapoxetine, a 5-HT selective reuptake inhibitor used for the treatment of premature ejaculation, have not been clearly identified. This study aimed to evaluate the effects of consumption of a high-fat meal and cytochrome P450 (CYP) 2D6 polymorphisms on the pharmacokinetics of dapoxetine in healthy Chinese men. Twenty-two healthy volunteers were enrolled and classified based on their CYP2D6 genotype. A single-dose, two-treatment (fasted and fed), two-period, one-sequence pharmacokinetic study was conducted. Plasma concentrations of the drug were determined using LC-MS. Pharmacokinetic parameters were calculated by a noncompartmental analysis. The consumption of food significantly prolonged the time required for dapoxetine to reach its peak concentration and area under the concentration-time curve (AUC0-48) (p < 0.01). Compared with that in *1/*10 and *2/*10 genotypes, the dapoxetine plasma exposure in *10/*10 individuals was notably increased. The AUC0-48 value for *10/*10 was significantly higher than that for *1/*10 and *2/*10 (p < 0.05). The obtained results demonstrated that a high-fat meal and the CYP2D6 *10/*10 genotype influence the pharmacokinetic properties of dapoxetine and may thus have potential clinical implications. Future studies focusing on safe dapoxetine dosing based on CYP2D6 genotyping are needed. This study was partially sponsored by Xiamen Fuman Pharmaceutical Co., Ltd. The article processing charges were funded by The People's Hospital of Dujiangyan City.