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DapoxetineSN,N-dimethyla21-naphthalenyloxy)ethylbenzenemethanamine hydrochlorideis a novel potent serotonin transport inhibitor with a unique pharmacokinetic profileand is currently in development for use in the treatment of PEDresser et al 2004Gengo et al 2005Dapoxetine hydrochloride is a water-soluble powder with a molecular weight of 341.88 and has a pKa of 8.6 and is mainly charged at a physiological pHThese pharmacological characteristics allow for rapid distribution in the body and are different from the pharmacokinetics observed in conventional SSRIsDapoxetine is a fast-acting compound that attains its peak plasma concentration in about 1.5 hours after dosingwhich is much faster than fluoxetineparoxetineor sertralineStrassberg et al 19992005Eli Lilly 2005GlaxoSmithKline 2005Pfizer 2005After oral administrationdapoxetine is readily absorbedfollowed by a rapid decline in plasma concentrationsThese pharmacokinetic properties make dapoxetine an excellent candidate for on-demand dosingwhich avoids the potential disadvantages of continuous pharmacotherapyThe pharmacokinetic characteristics of dapoxetine compared with paroxetine and sertraline are provided in Table 2

Recentlyin a well-designed studySalonia et al2002compared paroxetine alone with paroxetine and sildenafil as an oral therapy for men reporting PEIn the combination groupparoxetine was given as 10 mg once daily for 20 daysfollowed by 20 mg as needed and sildenafil 50 mg 1 hour before sexual activityThis study demonstrated that the combination of paroxetine and sildenafil obtained better results in regards to IELT and intercourse satisfaction than paroxetine aloneThe combination treatment was associated with a mild increase in drug-related adverse eventssuch as headache20nausea15and flushing15Despite the higher incidence of adverse effects associated with the combined therapymost patients90were willing to continue this treatment on an as-needed basis.

Dapoxetinea new option in the medical management of premature ejaculation.

There are three basic mechanisms involved in normal ante-grade ejaculationemissionexpulsionand orgasmand each of these components possesses separate neural pathwaysEjaculatory dysfunction can result from disruption of any point in this cascade of eventsSeveral recent studies have clarified some aspects of the physiology of ejaculationEmissionwhich begins with closure of the bladder neck to prevent retrograde flow of seminal fluid and sperm into the bladderrefers to the deposition of seminal fluid and sperm from the distal epididymisvas deferensseminal vesiclesand prostate into the posterior urethraWitt and Grantmyre 1993

Plasma concentration profiles of dapoxetine after administration of a single dose or multiple doses of dapoxetine 30 mgaand dapoxetine 60 mgbModi et al2006

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