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.

INTRODUCTION

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

FUNDING: 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.