Pharmacokinetics of dapoxetine hydrochloride in Chinese healthy male volunteers

SI Tian-mei; LIU Yi; SU Yu-nai; SUN Li-li; GUO Chun-mei; ZHANG Hong-yan; SHU Liang

doi:10.3321/j.issn:1003-3734.2009.22.010

Abstract：Objective: To explore the pharmacokinetics of dapoxetine hydrochloride tablets after a single o-ral administration in healthy Chinese male volunteers. Methods:24 subjects were randomly assigned to receive ei-ther a single oral dose of 30 mg or 60 mg dapoxetine. Sequential blood samples were collected, dopaxetine and its metabolites, desmethyldapoxetine, and dapoxetine-N-oxide in plasma were determined by a validated high perform-ance liquid chromatography with MS/MS. The pharmacokinetic parameters were calculated based on individual plasma concentration with noncompartmental analysis. Results: The demographic and baseline characteristics of subjects were well balanced between the 2 treatment groups. There were no early withdrawals and all 24 subjects completed the study. There was a rapid absorption of dapoxetine followed by abiphasic elimination of dapoxetine and its metabolites. Both the C_(max) and AUC of dapoxetine were proportional to dose following oral administration of single doses of 30 mg and 60 mg. The main pharmacokinetic parameters following oral administration of single doses of 30 mg and 60 mg were: C_(max) (204.0±71.4) and (396.0±27.2) μg·L~(-1), T_(max) (1.02±0.39) and (1.07± 0.28)h, t_(1/2)(15.0±7.2)and(15.4±5.8)h, AUC_(0～24)(901±338)and(1598±740) μg·h·L~(-1), and AUC_(0～∞) (1 078±508) and(2022±1107) μg·h·L~(-1). The dose-normalized AUCs and C_(max) of dapoxetine and its metabo-lites were similar. The ratios of parent compound to metabolites following oral administration of single doses of 30mg and 60 mg dapoxetine were as follows: C_(max) of N-oxide-dapoxetine (3.020±0.997) and (2.44±1.14), C_(max) of des-methyldapoxetine (23.8±3.57) and (20.3±5.54), AUC_(0～∞) of N-oxide-dapoxetine (0.794±0.279) and (0.670±0.292), AUC_(0～∞) of desmethyldapoxetine (7.99±1.79) and (8.28±2.21). The inter-subject variabili-ty was larger,the maximal CV% was 75.4%. The drug was well-tolerated. The most common adverse effects was transient and mild nausea and dizziness. Conclusion : Dapoxetine exposures following single-doses of 30 mg or 60 mg in Chinese male volunteers were generally similar to those in previous studies. Both the C_(max) and AUC of dapox-etine were increased with a dose-dependented manner, and the drug was well-tolerated.