Dapoxetine: Pharmacokinetics and Clinical Applications

General Description

Dapoxetine, marketed as Priligy, is an effective treatment for premature ejaculation due to its rapid absorption, short half-life, and minimal impact on norepinephrine and dopamine. Dapoxetine's pharmacokinetic profile allows for swift onset of action and consistent plasma concentrations with multiple doses. Clinical trials have shown significant improvement in Intravaginal Ejaculation Latency Time (IELT) with both 30 mg and 60 mg doses, leading to higher patient satisfaction levels. While some subjects discontinued treatment due to perceived lack of efficacy and mild adverse events like nausea and dizziness, dapoxetine remains a promising option for on-demand treatment of PE, especially considering its low prevalence of adverse events and lack of significant drug interactions.

Figure 1. Dapoxetine

Pharmacokinetics

Dapoxetine, marketed under the brand name Priligy by Menarini, Italy, exhibits a pharmacokinetic profile that distinguishes it as an effective treatment for premature ejaculation (PE). Structurally resembling fluoxetine, dapoxetine primarily targets the serotonin reuptake transporter, with minimal impact on norepinephrine and dopamine reuptake transporters. Its rapid absorption and water solubility facilitate swift onset of action. Following administration, dapoxetine undergoes biphasic elimination with initial and terminal half-lives of approximately 1.31-1.42 hours and 18.7-21.9 hours, respectively, for doses of 30 and 60 mg. This contrasts with longer-acting SSRIs like fluoxetine and paroxetine, which exhibit half-lives ranging from 16 to 96 hours. Dapoxetine reaches steady-state plasma concentrations within four days, considerably faster than fluoxetine's 1-22 months. Metabolized predominantly in the liver by cytochrome P450 isoenzymes CYP3A4 and CYP2D6, dapoxetine is primarily excreted in urine. Its metabolites include dapoxetine-N-oxide, desmethyldapoxetine, and didesmethyldapoxetine, with the latter two exhibiting similar efficacy to dapoxetine but in smaller percentages. Importantly, dapoxetine's pharmacokinetics remain consistent with multiple doses and are unaffected by co-administration with PDE-5 inhibitors, making it an ideal choice for on-demand treatment of PE. Unlike some SSRIs, dapoxetine does not induce significant increases in plasma concentrations with chronic use, ensuring rapid elimination post-treatment. In summary, dapoxetine's pharmacokinetic profile, characterized by rapid absorption, short half-life, and minimal accumulation, underscores its suitability for the effective management of PE with on-demand dosing. ¹

Clinical Applications

Dapoxetine, recognized for its rapid onset of action and short half-life, has emerged as a widely accepted treatment option for Premature Ejaculation (PE). Approved in over 50 countries, its on-demand usage has garnered popularity among patients seeking effective solutions for PE. Numerous randomized controlled trials (RCTs) spanning across more than 25 countries and involving over 6,000 men have substantiated dapoxetine's efficacy and safety. In these trials, dapoxetine demonstrated a significant increase in Intravaginal Ejaculation Latency Time (IELT) compared to placebo. Integrated analysis revealed that both 30 mg and 60 mg doses of dapoxetine resulted in geometric mean IELT improvements at 12 weeks. Moreover, patient-reported outcome measures indicated enhanced satisfaction levels with dapoxetine treatment. Interestingly, dapoxetine exhibited comparable effectiveness in men with both lifelong and acquired PE. However, despite its promising outcomes, a notable portion of subjects discontinued treatment, primarily due to perceived lack of efficacy and personal reasons. Adverse events associated with dapoxetine therapy were relatively common, albeit mostly mild to moderate in severity. Nausea, dizziness, headache, and diarrhea were among the frequently reported side effects. Notably, these adverse events led to treatment discontinuation, particularly among those on the 60 mg dose regimen. Despite these occurrences, dapoxetine's safety profile remains relatively favorable, with a low prevalence of adverse events noted in postmarketing observational studies. Moreover, no significant drug-drug interactions with dapoxetine have been reported, rendering it a viable option for patients with comorbid conditions such as Erectile Dysfunction (ED) who are already on a stable regimen of PDE5 inhibitors. In conclusion, dapoxetine stands as a promising therapeutic intervention for PE, offering rapid onset of action and meaningful improvements in IELT and patient-reported outcomes. However, clinicians should be mindful of potential adverse events and patient preferences when prescribing dapoxetine for PE management. ²

Reference

1. Modi NB, Dresser MJ, Simon M, Lin D, Desai D, Gupta S. Single- and multiple-dose pharmacokinetics of dapoxetine hydrochloride, a novel agent for the treatment of premature ejaculation. J Clin Pharmacol. 2006; 46(3): 301-309.

2. Sangkum P, Badr R, Serefoglu EC, Hellstrom WJ. Dapoxetine and the treatment of premature ejaculation. Transl Androl Urol. 2013; 2(4): 301-311.