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Dapoxetine (D) suffers from poor oral bioavailability (42%) due to extensive first pass metabolism. The usefulness of transmucosal (sublingual and intranasal) drug delivery to improve bioavailability of D, a weak basic drug, has been hampered by its poor solubility in the neutral pH of the body fluids. In this study, instantly-soluble transmucosal matrices (ISTMs) of D, containing dual mechanism solubilizer (Pluronic F-127/citric acid mixture), were prepared by lyophilization technique to enhance matrix disintegration, dissolution and transmucosal permeation. The matrices were evaluated for in-vitro disintegration, wetting time, in-vitro dissolution, ex vivo transmucosal permeation, scanning electron microscopy and in-vivo studies. Dissolution studies confirmed the higher ability of ISTMs to enhance the early time point dissolution and maintain complete drug dissolution in pH 6.8 compared to conventional lyophilized matrices. The optimized ISTM gave approximately 77.54 and 88.40 folds increase of D dissolution after 1 and 3min relative to the drug powder in pH 6.8. ISTMs containing the highest F127 concentration (2%) and the lowest gelatin and mannitol concentrations (1%) exhibited the shortest in-vitro disintegration times (<10s), the fastest dissolution in the neutral pH of body fluids (∼99% in 3min) and the highest enhancement of transmucosal permeation. The relative bioavailabilities of D after sublingual and intranasal administration of ISTMs to rabbits were about 124.58% and 611.15%, respectively, in comparison to the oral market tablet. The significant increase of drug dissolution in nasal fluids, rapid permeation rate together with the improved bioavailability propose that ISTMs could be promising for intranasal delivery of drugs suffering from oral hepatic metabolism and have limited solubility in nasal fluids., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Dapoxetine is a short-acting selective serotonin reuptake inhibitor for treatment of premature ejaculation (PE)., Aim: To evaluate the efficacy and safety of dapoxetine 30 and 60 mg as needed in Asia-Pacific men with PE., Methods: The study was a prospective, 12-week, open-label study to evaluate the efficacy and safety of flexible-dose dapoxetine in men with PE diagnosed by a Premature Ejaculation Diagnostic Tool score of at least 11, a self-estimated intravaginal ejaculation latency time (IELT) no longer than 2 minutes, and an International Index of Erectile Function erectile function domain score of at least 21., Main Outcome Measures: Percentage of subjects reporting their PE as at least "slightly better" using the Clinical Global Impression of Change (CGIC) question., Results: Two hundred eighteen of 285 randomized subjects completed the study. The mean subject age was 45.9 years and 57.7% were Korean. Dosages 1 (30 mg), 2 (30 → 60 mg), and 3 (30 → 60 → 30 mg) were used in 141, 124, and 13 subjects, respectively. At study end, a PE CGIC rating of at least "slightly better" was reported by 77.3%, 92.8%, and 100% of subjects for dosages 1, 2, and 3, respectively (P = .49). At study end, a CGIC rating of "slightly better" was reported by 85.2% and 85.3% of subjects with lifelong PE and acquired PE, respectively (P = .50). At study end, a CGIC rating of "slightly better" was reported by 84.1% and 86.4% of subjects with an estimated baseline IELT no longer than and at least ≤1 minute, respectively (P = .16). The incidence of a CGIC rating of at least "slightly better" was lower in subjects reporting an adverse event of moderate or severe severity and in subjects who increased to and maintained a dapoxetine dose of 60 mg and higher in subjects older than 50 years and in subjects with a baseline estimated IELT of at least 1 minute., Conclusion: In this study, flexible dosing of dapoxetine (30 and 60 mg) appeared effective in the treatment of PE., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the pharmacokinetic interaction of Epimedium extract on the dapoxetine in rats. Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10mg/kg, i.v.); (2) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, i.v.); (3) dapoxetine alone (10mg/kg, p.o.); (4) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, p.o.). The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500ng/mL with the R(2)=0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rats. The oral bioavailability of dapoxetine was about 75% in rats., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: CYP2D6 is one of the most important members of the cytochrome P450 superfamily. Its genetic polymorphism significantly influences the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure., Methods and Results: The aim of this research was mainly to explore the catalytic activities of 22 newly reported CYP2D6 isoforms (2D6*87, *88, *89, *90, *91, *92, *93, *94, *95, *96,*97, *98, *R25Q, F164L, E215K, F219S, V327M, D336N, V342M, R344Q, R440C, R497C) on dapoxetine in vitro. The research was designed with an appropriate incubation system in test tubes and carried out in the constant temperature water. Through detecting its two metabolites desmethyldapoxetine and dapoxetine-N-oxide, the available data were obtained to explain the influence of CYP2D6 polymorphism on the substrate drug dapoxetine. As a result, the intrinsic clearance (Vmax/Km) values of most variants were significantly altered when compared with the counterpart of CYP2D6*1, with most of these variants exhibiting either reduced Vmax and/or increased Km values. For dapoxetine demethylation pathway (which produces desmethyldapoxetine), 2D6*89 and E215K exhibited no markedly decreased relative clearance of 92.81% and 97.70%, respectively. The relative clearance of rest 20 variants exhibited decrease in different levels, ranging from 20.44% to 90.90%. For the dapoxetine oxidation pathway (which produces dapoxetine-N-oxide), the relative clearance values of three variants, 2D6*90, *94, and V342M, exhibited no markedly increased relative clearance of 106.17%, 107.78%, and 109.98%, respectively; the rest 19 variants exhibited significantly decreased levels ranging from 27.56% to 84.64%. In addition, the kinetic parameters of two CYP2D6 variants (2D6*92 and 2D6*96) could not be detected, due to the defect of the CYP2D6 gene., Conclusion: As the first report of all aforementioned alleles for dapoxetine metabolism, these data may help in the clinical assessment of the metabolic elimination of dapoxetine and may provide fundamental information for further clinical studies.

A sensitive and rapid ultra performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) method was developed to determine dapoxetine and its two major metabolites (dapoxetine-N-oxide and desmethyldapoxetine) in human plasma simultaneously. After a simple protein precipitation, the analytes and the combined internal standard (carbamazepine) were separated on an Acquity UPLC BEH C18 column using a mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution. Mass spectrometric analysis was performed using a XEVO TQD triple quadruple mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions are of m/z 306.3→261.2, m/z 322.2→261.2, m/z 292.2→261.2 and m/z 237.1→194.2 for dapoxetine, dapoxetine-N-oxide, desmethyldapoxetine and IS, respectively. The linearity of this method was found to be within the concentration range of 1.0-200ng/mL for dapoxetine; 0.5-100ng/mL for dapoxetine-N-oxide; and 0.1-5.0ng/mL for desmethyldapoxetine in human plasma, respectively. Only 4.0min was needed for an analytical run. Intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all of the concentrations. This assay was successfully used to support a clinical pharmacokinetic study following oral administration of dapoxetine tablets in healthy Chinese subjects., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: Dapoxetine (DPX) has a pharmacokinetic profile suggesting a low rate of class-related adverse events (AEs)., Aim: To assess the incidence of treatment emergent AEs (TEAEs) of special interest (known associations with selective serotonin reuptake inhibitors and/or potential clinically relevant AEs), and the related discontinuation rate in patients with premature ejaculation (PE) treated with DPX or alternate oral treatment (AOT), in routine clinical practice., Methods: In a prospective, 12-week, open-label, postmarketing observational, multinational study (PAUSE), 7545 patients were enrolled and divided into 2 groups: DPX 30-60 mg and AOT., Main Outcome Measures: The incidence rate of predefined TEAEs of special interest (mood and related, neurocognitive related, cardiovascular, urogenital and sexual function, accidental injury, and abnormal bleeding) in the DPX and the AOT groups, and the rate of AEs leading to study discontinuation., Results: The safety analysis was performed on 6128 patients treated with DPX and 1417 with AOT. The incidence of TEAEs of special interest in each AE category was greater for patients treated with AOT than with DPX. The higher differences were observed in the neurocognitive-related category (DPX 1.9% vs. AOT 4.7%; P < .001), in the mood and related category (DPX 0.4% vs. AOT 1.1%; P < .001), and in the urogenital system/sexual function (DPX 0.4% vs. AOT 0.8%; P = .04). Cardiovascular TEAEs were the only AEs numerically greater in the DPX group (1.3 vs. 1.6%, P = .34). The overall discontinuation rate was 10.9% in the DPX group and 6.9% in the AOT group)., Conclusion: DPX has a favorable safety profile in terms of class-related TEAEs and clinically relevant AEs of special interest. In particular, it shows a significantly better safety profile in mood and related AEs, neurocognitive-related AEs, urogenital system, and sexual function, compared to the AOT group in the study population., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Human semen contains spermatozoa secreted by the testes and a mixture of components produced by the bulbo-urethral and Littre (paraurethral) glands, prostate, seminal vesicles, ampulla, and epididymis. Ejaculation is used as a synonym for the external ejection of semen, but it comprises two phases: emission and expulsion. As semen collects in the prostatic urethra, the rapid preorgasmic distension of the urethral bulb is pathognomonic of impeding orgasm, and the man experiences a sensation that ejaculation is inevitable (in women, emission is the only phase of orgasm). The semen is propelled along the penile urethra mainly by the bulbocavernosus muscle. With Kegel exercises, it is possible to train the perineal muscles. Immediately after the expulsion phase the male enters a refractory period, a recovery time during which further orgasm or ejaculation is physiologically impossible. Age affects the recovery time: as a man grows older, the refractory period increases. Sexual medicine experts consider premature ejaculation only in the case of vaginal intercourse, but vaginal orgasm has no scientific basis, so the duration of intercourse is not important for a woman's orgasm. The key to female orgasm are the female erectile organs; vaginal orgasm, G-spot, G-spot amplification, clitoral bulbs, clitoris-urethra-vaginal complex, internal clitoris and female ejaculation are terms without scientific basis. Female sexual dysfunctions are popular because they are based on something that does not exist, i.e. the vaginal orgasm. The physiology of ejaculation and orgasm is not impaired in premature ejaculation: it is not a disease, and non-coital sexual acts after male ejaculation can be used to produce orgasm in women. Teenagers and men can understand their sexual responses by masturbation and learn ejaculatory control with the stop-start method and the squeeze technique. Premature ejaculation must not be classified as a male sexual dysfunction. It has become the center of a multimillion dollar business: is premature ejaculation-and female sexual dysfunction-an illness constructed by sexual medicine experts under the influence of drug companies?, (© 2015 Wiley Periodicals, Inc.)

Conventional theories and therapies for premature ejaculation (PE) are based on assumptions not always supported by evidence. This review of the current literature on the physiology of the ejaculatory control, pathogenesis of PE, and available therapies shows that PE is still far from being fully understood. However, several interesting hypotheses have been formulated, and solid, evidence-based clinical data are currently available for dapoxetine, the unique, first-line, officially approved pharmacotherapy for PE. Further growth in the field of PE will occur only when we shift from opinion-based classifications, definitions, and hypotheses to robust, noncontroversial data grounded on evidence., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: It is not known whether the efficacy of dapoxetine, the only drug approved for the on-demand treatment of premature ejaculation (PE), can be increased by the addition of sexual behavioral treatment (SBTx)., Aim: To test the hypothesis that combined dapoxetine and SBTx provide better result than dapoxetine alone in the management of patient with lifelong PE., Methods: After a 4-week run-in period, 50 patients with lifelong PE entered a 24-week, open-label, prospective study with a 1:1 assignment. Twenty-five patients (group A) received on-demand dapoxetine 30 mg alone, and the remaining 25 patients (group B) combined on-demand dapoxetine 30 mg and SBTx. The CONSORT 2010 statement was adhered to where possible., Main Outcome Measures: The intravaginal ejaculatory latency time (IELT), the premature ejaculation diagnostic tool (PEDT) score, and the treatment-emergent adverse events (TEAEs) were analyzed., Results: Mean age was 34.16 years in group A and 34.44y in group B. From baseline to 4-, 12- and 24-week evaluation, both groups experienced a significant (P < 0.0001) increase in mean IELT and decrease in mean PEDT score, but patients in group A showed a significantly lower increase in mean IELT (85.0; 84.8; 130.7; 160.0 vs. 92.0; 137.9; 232.7; 370.7 seconds, respectively; P < 0.0001) and a significantly lower decrease in mean PEDT score (20.4; 18.16; 15.88; 14.68 vs. 19.56; 16.0; 11.96; 7.92, respectively; P < 0.0001) than those in group B. At 24-week evaluation, no patient in group A reached a PEDT score ≤8 (absence of PE) as opposed to 80% of patients in group B. There was no difference between groups in TEAEs rate (16% vs. 16%; P = 1.00). Limitations included the absence of a group receiving SBTx alone or group crossover., Conclusions: Combined dapoxetine and SBTx proved to be more effective than dapoxetine alone in treating patients with lifelong PE, up to restoring a normal ejaculatory function in most of them., (© 2015 International Society for Sexual Medicine.)

Premature ejaculation (PE) is the most prevalent male sexual dysfunction. This is associated with negative personal and interpersonal psychological outcomes. The pharmacologic treatment of PE includes the use of antidepressants, local anesthetic agents, and phosphodiesterase type 5 inhibitors. While numerous treatments can control PE, only antidepressants and topical anesthetic creams and sprays have recently been shown to be more effective. This review focuses on the physiology and pharmacology of ejaculation, the pathophysiology of PE and the most effective pharmacological treatment of PE. Pharmacotherapy of PE with off-label short-acting selective serotonin reuptake inhibitors (SSRIs) is common, effective, and safe. Dapoxetine, a SSRI with a short half-life, has been recently evaluated for the treatment of PE by several countries and results are promising. In clinical practice, follow-up side effects are an important part of the management strategy for PE. The understanding of etiology, pathophysiology, and treatment modalities of PE would be beneficial to clinician in helping patients with this disappointing sexual problem., (© 2015 American Society of Andrology and European Academy of Andrology.)

Purpose: Dapoxetine is the first oral agent approved for the treatment of premature ejaculation (PE). However, some countries have not approved its use. The goal of this meta-analysis was to provide more information about the efficacy and safety of dapoxetine in patients with PE., Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing dapoxetine with a placebo in patients with PE. Relevant eligible RCTs were identified through comprehensive searches of the Cochrane Central Register of Controlled Trials, EMBASE, and PubMed. Efficacy (intravaginal ejaculatory latency time (IELT), patient global impression of change, perceived control over ejaculation, and satisfaction with sexual intercourse) and safety (treatment-emergent adverse events and discontinuation rates) were studied by using Review Manager version 5.1.0., Findings: Six RCTs involving 5934 patients met the inclusion criteria. The main outcome (IELT) in the dapoxetine group was improved significantly compared with IELT in the placebo group (mean difference, 1.59 [95% CI, 1.30 to 1.88]; P < 0.00001). The 60-mg dose of dapoxetine was more beneficial than the 30-mg dose for IELT (mean difference, -0.47 [95 % CI, -0.73 to -0.20]; P = 0.0005). Although the occurrence of treatment-emergent adverse events in the dapoxetine group was nearly twice that in the placebo group (50.5% vs 27.9%), reports of severe adverse events were rare., Implications: Data from the meta-analysis revealed that treatment with dapoxetine was significantly efficacious in patients with PE. Although adverse events such as nausea, dizziness, diarrhea, insomnia, and headache were common, dapoxetine's overall safety profile was acceptable., (Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.)

Strategies, recommendations and techniques proposed by sex therapy for intervention on premature ejaculation, have represented for nearly four decades the most effective model of intervention in this sexual dysfunction, which currently is complemented by the efficacy of dapoxetine drug treatment. Clinical experience and recent studies support that combined intervention offers the best therapeutic results. In addition in sex therapy, etiologic diagnosis is obtained from the analysis of the interrelationship of the couple. Diagnostic and therapeutic intervention has to be always centered in the relationship, so the techniques and resources must be applied with the expectation of being implemented in the sexual interaction. It will therefore be the relationship that receive treatment, even if medication is used for one of the members of the couple. On the other hand, this model of intervention can be implemented by a professional with training, although not necessarily a specialist., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.)

Biomedical approach to premature ejaculation (PE) has permited a better phisiopatologycal knowledge and so the use of pharmacological agents for the treatment of this sexual dysfuncion. Most of the studies to evaluate the eficacy of these drugs were not carried at all the parameters which actually define PE: intravaginal ejaculatory latencie time (IELT) tested with watch, ejaculation control self perception cuantification (questionaries) and cuantification of generated consequences in patient and partner, if it existes. For this reason, it is difficult to analyse the scientific evidence and we use medicines with no approved indication for PE ("off label"). This text is a review of pharmacologycal agents with no approved indication (PDE type 5 inhibitors, α-blockers, tramadol, SSRI, clomipramine), and pharmacologycal agents developed to be used in the treatment of PE and having got indication in this sexual dysfunction or "on label" drugs (topic anesthesics, dapoxetine)., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.)

Premature ejaculation (PE) is a common male sexual disorder. It is defined by the Diagnostic and statistical manual of mental disorders as "ejaculation occurring, without control, on or shortly after penetration and before the person wishes it, causing marked distress or interpersonal difficulty.([1]) Although the timing of intravaginal ejaculatory latency time (IELT) (i.e., time from penetration to ejaculation) is not included in this definition, an IELT of <2 min, or ejaculation occurring before penetration, has been considered consistent with PE.([2]) Management involves both the patient and his partner. Therapeutic options should suit both partners and be appropriate to their habit in planning and frequency of intercourse. Follow-up at appropriate intervals to judge efficacy, titrate dosage of pharmacological treatments and ascertain side effects is mandatory.

Background: Premature ejaculation (PE) is the most common male sexual complaint. Off-label oral selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of PE. Dapoxetine is a short-acting SSRI specifically designed for on-demand use. The objective of this communication is to summarize the clinical and physiological evidence regarding the role of the serotonergic pathway and specifically dapoxetine in the treatment of PE., Methods: A PubMed search was conducted on articles reporting data on dapoxetine for the treatment of PE. Articles describing the pathophysiology and treatment options for PE were additionally included for review., Results: The etiology of PE is multi-factorial in nature. There are many treatment options for PE such as psychological/behavioral therapy, topical anesthetic agents, phosphodiesterase type 5 (PDE-5) inhibitors, and tramadol hydrochloride. SSRIs play a major role in PE treatment. Animal and clinical studies in addition to its pharmacokinetic document dapoxetine's clinical efficacy and safety for on-demand treatment of PE., Conclusions: Dapoxetine demonstrates clinical efficacy and a favorable side effect profile. Dapoxetine is currently the oral drug of choice for on-demand treatment of PE.

Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological consequences. Pharmacotherapy of PE with off-label antidepressant selective serotonin reuptake inhibitors (SSRIs) is common, effective and safe. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill an unmet treatment need. The objective of this article is to review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE. MEDLINE, Web of Science, PICA, EMBASE and the proceedings of major international and regional scientific meetings were searched for publications or abstracts published during the period 1993-2012 that used the word 'dapoxetine' in the title, abstract or keywords. This search was then manually cross referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase I, II and III studies, independent postmarketing and pharmacovigilance efficacy and safety studies and drug-interaction studies. Dapoxetine is a potent SSRI which is administered on demand 1-3 h prior to planned sexual contact. It is rapidly absorbed and eliminated, resulting in minimal accumulation, and has dose-proportional pharmacokinetics which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in five industry-sponsored randomized, double-blind, placebo-controlled studies in 6081 men aged at least 18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, Clinical Global Impression of Change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine versus placebo (all p <0.001). The most common treatment-related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (5.9% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use. Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.

Premature ejaculation (PE) is a major issue in male sexual health. The global prevalence of PE is estimated to be between 20% and 40%, making it the most common sexual dysfunction in men. PE causes distress and reduced quality of life for patients and has a negative impact on interpersonal relationships. Historically, it has been treated with cognitive therapy, behavioral methods, and off-label use of selective serotonin reuptake inhibitors usually used to treat depression and other psychological disorders. Dapoxetine is a selective serotonin reuptake inhibitor specifically designed to treat PE. This paper reviews the current evidence for use of dapoxetine in the treatment of PE in adult men. There is substantial evidence that dapoxetine 30 mg or 60 mg taken "on-demand" results in a significant increase in intravaginal ejaculatory latency time when compared with placebo. Patient-reported outcomes are clearly improved relative to placebo following dapoxetine therapy, indicating greater control over ejaculation, more satisfaction with intercourse, less ejaculation-related distress, and, importantly, significantly reduced interpersonal difficulty. These data were supported by consistent reports of improvement in Clinical Global Impression of change in PE following treatment with dapoxetine. Further studies are needed to evaluate long-term efficacy and health economics. The unique pharmacology of dapoxetine makes it ideal for on-demand dosing, and the clinical evidence shows dapoxetine to be an efficacious and tolerable treatment for lifelong and acquired PE.

Introduction: Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological factors. Pharmacotherapy of PE with off-label antidepressant SSRI drugs is common. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill a unmet treatment need., Aim: To review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE., Methods: MEDLINE and the proceedings of major international and regional scientific meetings during the period 1994-2010 were searched for publications or abstracts using the word dapoxetine in the title, abstract or keywords. This search was then manually cross-referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase 1, 2 and 3 efficacy and safety studies and drug-interaction studies., Results: Dapoxetine is a potent selective serotonin re-uptake inhibitor, which is administered on-demand 1-3 hours prior to planned sexual contact. Dapoxetine is rapidly absorbed and eliminated, resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in 5 randomized, double-blind, placebo-controlled studies in 6081 men aged ≥18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, clinical global impression of change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P < 0.001 for all). The most common treatment related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (586% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use., Conclusion: Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.

Premature ejaculation (PE) is a common problem in men worldwide. It has a significant impact on affected men and their partners in terms of self-esteem, dissatisfaction with their sexual relationships, personal distress, and interpersonal difficulty. Psychological therapies may achieve short-term improvements, but there are limited data on the long-term success of these methods. Oral therapy with long-acting selective serotonin reuptake inhibitors (SSRIs) improves intravaginal ejaculatory latency time (IELT), but these agents are designed to be administered daily and may be associated with unwanted sexual side effects and withdrawal symptoms upon abrupt discontinuation. Dapoxetine is a short-acting SSRI that can be taken as needed (prn) by men with PE. It has been studied in five separate multicenter, randomized, double-blind, placebo-controlled trials involving more than 6000 men with PE. In four studies that evaluated IELT as an endpoint (N = 4843), dapoxetine 30 and 60 mg prn achieved statistically significant increases in IELT versus placebo. Dapoxetine also showed statistically significant improvements in perceived control over ejaculation, PE-related personal distress, and other patient-reported outcomes in all five trials. Dapoxetine treatment is generally well-tolerated, with low incidences of discontinuation syndrome, sexual dysfunction, and treatment-emergent mood symptoms. The most common adverse events with dapoxetine included nausea, diarrhea, headache, dizziness, and somnolence.

Premature ejaculation (PE) is a common male sexual disorder. Recent normative data suggest that men with an intravaginal ejaculatory latency time (IELT) of less than 1 minute have "definite" PE, while men with IELTs between 1 and 1.5 minutes have "probable" PE. Although there is insufficient empirical evidence to identify the etiology of PE, there is limited correlational evidence to suggest that men with PE have high levels of sexual anxiety and inherited altered sensitivity of central 5-HT (serotonin) receptors. Pharmacological modulation of the ejaculatory threshold using off-label daily or on-demand selective serotonin re-uptake inhibitors (SSRIs) offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treatment, consequential improvements in sexual desire and other sexual domains and is well tolerated. Investigational drugs such as the ejaculo-selective serotonin transport inhibitors (ESSTIs) such as dapoxetine and UK-390,957 represent a major development in sexual medicine. These drugs offer patients the convenience of on-demand dosing, significant improvements in IELT, ejaculatory control, and sexual satisfaction with minimal adverse effects.