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

Abstract

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:

RETRACTED ARTICLE: Safety and Efficacy of Dapoxetine in the Treatment of Premature Ejaculation: A Double-Blind, Placebo-Controlled, Fixed-Dose, Randomized Study

“…The mean initial half-life of dapoxetine after a single dose is 0.5-0.8 h, and this decreases slightly to 0.4-0.6 h after multiple doses for 6 days. The terminal half-life of dapoxetine is 15-19 h after a single dose and 20-24 after multiple doses (Dresser et al, 2004).…”

Dapoxetine: a new option in the medical management of premature ejaculation

“…Dapoxetine undergoes rapid absorption and elimination resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing and do not vary between ethnic groups (Figure 2) [Dresser et al 2006b;Dresser et al 2004;Modi et al 2006]. The pharmacokinetic profile of dapoxetine suggests that it is a good candidate for on-demand treatment of PE.…”

“…Dapoxetine is extensively metabolized in the liver by multiple isozymes to multiple metabolites, including desmethyldapoxetine, didesmethyldapoxetine and dapoxetine-n-oxide, which are eliminated primarily in the urine [Dresser et al 2004;Modi et al 2006]. Although didesmethyldapoxetine is equipotent to the parent dapoxetine, its substantially lower plasma concentration, compared with dapoxetine, limits its pharmacological activity and it exerts little clinical effect, except when dapoxetine is coadministered with cytochrome P450 3A4 (CYP3A4) or CYP2D6 inhibitors.…”

“…In a randomized, double-blind, placebo-controlled trial, single doses and multiple doses over 6 days of dapoxetine (60, 100, 140, or 160 mg) were administered to 77 healthy male volunteers [Dresser et al 2004[Dresser et al , 2006bThyssen et al 2010]. Dapoxetine has a T max of 1.4-2.0 h and rapidly achieves peak plasma concentration (C max ) following oral administration.…”

“…At all doses, dapoxetine significantly reduced the proportion of rats displaying PCA-induced ejaculation in a dose-dependent manner, from 78% of rats with vehicle to 33%, Table 1. Pharmacokinetics of single doses of dapoxetine (30 mg, 60 mg) and effect of food on pharmacokinetics [Dresser et al 2004[Dresser et al , 2006bModi et al 2006 …”