Pharmacokinetics of Dapoxetine, a New Treatment for Premature Ejaculation: Impact of Age and Effects of a High‐Fat Meal

Abstract

Dapoxetine is being developed as a treatment for premature ejaculation and has demonstrated rapid absorption and elimination in previous pharmacokinetic studies. Two open-label studies were conducted in healthy men: a parallel-group pharmacokinetic and safety study in young and elderly men and a randomized crossover food-effect study. Maximal plasma dapoxetine concentrations (C(max)) were similar in young and elderly men (338 and 310 ng/mL, respectively), as were the corresponding area under the plasma concentration versus time curve (AUC) values (2040 and 2280 ng x h/mL, respectively). When coadministered with food, C(max) was reduced by 11% (398 vs 443 ng/mL in the fed and fasted states, respectively), and the peak was delayed by approximately 30 minutes, indicating that food slowed the rate of absorption; however, systemic exposure to dapoxetine (ie, AUC) was not affected by food consumption. Thus, age or consumption of a high-fat meal has only a modest impact on dapoxetine pharmacokinetics in healthy men.

Cardiovascular Safety Profile of Dapoxetine during the Premarketing Evaluation

“…[17][18][19] Dapoxetine demonstrates rapid absorption and elimination, reaching C max within 1.5 hours of administration, plasma concentrations are less than 5% of peak at 24 hours, and there is minimal accumulation following daily dosing. [7][8][9] In comparison, other SSRI medications have relatively slower absorption, and lack the rapid initial elimination phase that is a characteristic of dapoxetine, resulting in potentially longer periods of exposure and accumulation. [8,24,44,45] The premarketing evaluation of dapoxetine provided a comprehensive assessment of the cardiovascular safety of dapoxetine.…”

“…[1,2] Although sexual activity has been identified as a potential cardiac risk factor in patients with pre-existing cardiovascular disease, [3] PE has CURRENT OPINION Drugs R D 2011; 11 (1): [1][2][3][4][5][6][7][8][9][10][11] 1179-6901/11/0001-0001 not been associated with any cardiovascular comorbidities or health risks. [4] Dapoxetine is a novel selective serotonin reuptake inhibitor (SSRI) developed as an ondemand oral treatment for PE and has been granted marketing authorization for the treatment of PE in men aged 18-64 years in 15 countries (as of August 2010).…”

“…Dapoxetine demonstrates rapid absorption and elimination with minimal accumulation following daily dosing, and is extensively metabolized by multiple enzymes. [7][8][9] Other SSRI medications approved for the treatment of depression have been shown to delay ejaculation in patients being treated for depression [10,11] and are used as off-label treatment for PE. [12,13] In comparison with dapoxetine, other SSRI medications have relatively slower absorption, resulting in potentially longer periods of exposure and accumulation.…”

Electrochemical Determination of Dapoxetine HCl in Biological Fluids Using Coated Wire Electrod

“…This drug is mainly useful in erectile dysfunction as SSRI (selective serotonin reuptake inhibitor) and it is the first drug approved for the on-demand treatment of premature ejaculation in men [1]. The chemical structure of DAP is shown in Fig.…”

Premature Ejaculation Re-Visited: Definition and Contemporary Management Approaches

“…In fact, it has received regulatory approval as an ondemand treatment for PE in several parts of the world . In contrast to conventional SSRIs, maximum plasma concentrations are achieved 1.01 h after a 30-mg oral dose, initial half-life is 1.42 h and 24 h after administration, plasma concentrations decrease to less than 5% of peak levels (Dresser et al, 2006). Pryor et al published an integrated analysis of two double-blind, randomised controlled trials to determine the efficacy and tolerability of dapoxetine in the treatment of PE (Pryor et al, 2006).…”