Pharmacokinetics of single and multiple escalating doses of dapoxetine in healthy volunteers

Objective To characterize the pharmacokinetics and safety of single and multiple doses of dapoxetine, a novel agent under development for the treatment of premature ejaculation, a urogenital disorder. Methods: This was a randomized, double-blind, placebo-controlled, single and multiple dose study in 77 healthy male volunteers. Dapoxetine was administered orally as a single dose of 60, 100, 140, or 160 mg or once-daily for 6 days at 80, 100, or 120 mg. Pharmacokinetic parameters were determined by non-compartmental methods. Safety was evaluated by physical exam; laboratory, vital signs and ECG measurements; and monitoring of adverse events. Results: Dapoxetine was quickly absorbed with peak plasma concentrations occurring at ~1.5 h after dosing followed by a rapid decline in plasma concentrations. Cmax and AUC increased proportionally up to 100 mg. Dapoxetine had a terminal half-life of ~18 h. Single- and multiple-dose pharmacokinetics were comparable. No serious adverse events were reported, and there were no clinically relevant changes in any clinical laboratory tests, vital signs, or ECG. Nausea, the most common adverse event, was mild or moderate. Conclusions: Following oral administration, dapoxetine was rapidly absorbed; a fast decline in plasma concentrations followed. Dapoxetine was well tolerated following single and multiple doses to healthy volunteers. Clinical Pharmacology & Therapeutics (2004) 75, P32–P32; doi: 10.1016/j.clpt.2003.11.123