Dapoxetine Hydrochloride

Dapoxetine is a short‐acting selective serotonin reuptake inhibitor used to treat premature ejaculation. However, its clinical effectiveness is challenged by substantial inter‐individual variability in pharmacokinetics, as both the drug's therapeutic efficacy and the incidence of adverse reactions are highly dependent on its exposure. This study aims to develop a population pharmacokinetic model for dapoxetine, to investigate the sources of the variability, and to identify demographic and pharmacogenetic factors that influence drug exposure. The pharmacokinetic data for this analysis were obtained from a bioequivalence study conducted in 39 healthy Chinese male subjects. As part of this study, all volunteers were genotyped for the CYP3A4*1G, CYP3A5*3, CYP2D6*10, and CYP2D6*41 allelic variants. Population pharmacokinetic modeling was performed in Monolix. The final model was then used to simulate and compare the effect of different covariate levels on dapoxetine exposure. A two‐compartment model with first‐order absorption and an absorption lag time best described the pharmacokinetics of dapoxetine. The population parameters for apparent clearance (CL/F), apparent intercompartmental clearance (Q/F), apparent central volume of distribution (Vc/F), apparent peripheral volume of distribution (Vp/F), absorption lag time (Tlag), and absorption rate constant (ka) were 37.8 L/h, 17.2 L/h, 65.6 L, 191.7 L, 0.68 h, and 1.29/h, respectively. CYP2D6*10 and CYP2D6*41 alleles were found to be significant covariates on CL/F. The CYP3A4*1G allele influenced Q/F, while body mass index (BMI) was a significant covariate on Vc/F. Our analysis identified CYP2D6*10 and CYP2D6*41 polymorphisms as the significant factors contributing to inter‐individual variability and influencing drug exposure.

Recent research has highlighted the potential advantages of combining pharmacologic and non-pharmacologic approaches in treating lifelong premature ejaculation (LPE). Individual therapies have demonstrated efficacy but there is a lack of comprehensive analysis comparing combined treatments to pharmacologic monotherapy.

To assess the combined effect of dapoxetine with non-pharmacological therapies compared to drug monotherapy in improving ejaculatory latency, functionality, and self-perception of sexual dysfunction in individuals with LPE.

A systematic search was performed in PubMed, PEDro, Cochrane, Web of Science, CINAHL, and Academic Search Ultimate databases from inception to October 2024 to identify randomized controlled trials (RCTs). The primary outcome was the intravaginal ejaculatory latency time (IELT), while secondary outcomes were self-perception improvements, assessed using the Premature Ejaculation Diagnostic Tool (PEDT), the premature ejaculation profile (PEP), and other evaluation instruments.

Eight RCTs (n = 656 participants) were included. Pooled analysis of studies showed a significant effect of dapoxetine combined with non-pharmacological therapies in improving IELT compared to dapoxetine monotherapy (SDM = 1.6; 95%CI, 0.5-2.8; P = .01), PEDT scores (SDM = 0.9; 95%CI, 0.4-1.4; P < .001) and PEP subscales, with moderate certainty of evidence according to the GRADE guidelines. The non-pharmacological therapies included shockwave therapy, biofeedback, electric stimulation, pelvic floor muscle training, desensitization techniques, psychotherapy, and behavioral therapy.

This systematic review and meta-analysis indicate that while dapoxetine is recognized for its beneficial effects, its clinical efficacy is significantly enhanced when combined with non-pharmacological interventions. Combination therapy increases IELT, reduces PEDT scores, and improves PEP scores. These findings suggest that combination therapy is more effective than dapoxetine monotherapy in improving functional outcomes and self-perception in patients with LPE, supported by moderate certainty of evidence.