Single‐ and Multiple‐Dose Pharmacokinetics of Dapoxetine Hydrochloride, a Novel Agent for the Treatment of Premature Ejaculation

Dapoxetine is a serotonin transporter inhibitor currently in development for the treatment of premature ejaculation. This randomized, 2‐sequence, 2‐treatment crossover study assessed the single‐ and multiple‐dose pharmacokinetics of dapoxetine following once‐daily administration of dapoxetine 30 mg and 60 mg to healthy male volunteers. Dapoxetine was rapidly absorbed following oral administration, with peak plasma concentrations reached approximately 1 hour after dosing; plasma concentrations after single doses of dapoxetine decreased rapidly to approximately 5% of peak concentrations by 24 hours. Elimination was biphasic, with an initial half‐life of approximately 1.4 hours and a terminal half‐life of approximately 20 hours. Dapoxetine showed time‐invariant pharmacokinetics and dose proportionality between doses, and its pharmacokinetics was unaffected by multiple dosing. The pharmacokinetics of dapoxetine metabolites, desmethyldapoxetine and dapoxetine‐N‐oxide, was similarly unaffected by multiple dosing. There were no serious adverse events; the most commonly reported adverse events were diarrhea, dizziness, and nausea.