1. ¹ALZA Corporation, Mountain View, CA, USA
2. ²Department of Urology, University Hospital of Cleveland, Case Western Reserve University, Cleveland, OH, USA

Correspondence: Mark J Dresser, Clinical Pharmacology, ALZA Corporation, 1900 Charleston Road, Building M11, Mountain View, CA 94043, USA. E-mail: mdresser@alzus.jnj.com

Received 10 June 2005; Revised 23 August 2005; Accepted 19 October 2005; Published online 24 November 2005.

Abstract

Potential pharmacokinetic interactions between dapoxetine, a serotonin transporter inhibitor developed for the treatment of premature ejaculation (PE), and the phosphodiesterase-5 inhibitors tadalafil and sildenafil, agents used in the treatment of erectile dysfunction (ED), were investigated in an open-label, randomized, crossover study (n=24 men) comparing dapoxetine 60 mg, dapoxetine 60 mg+tadalafil 20 mg, and dapoxetine 60 mg+sildenafil 100 mg. Plasma concentrations of dapoxetine, tadalafil, and sildenafil were determined by liquid chromatography–tandem mass spectrometry. Tadalafil did not affect the pharmacokinetics of dapoxetine, whereas sildenafil increased the dapoxetine AUC_inf by 22%; these effects were deemed not clinically important. Dapoxetine did not appear to affect the pharmacokinetics of tadalafil or sildenafil. Most adverse events were mild in nature. Thus, dapoxetine has no clinically important pharmacokinetic interactions with tadalafil or sildenafil, and the combinations are well tolerated.