Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors.
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 AUCinf 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.
Dresser
M J
MJ
ALZA Corporation, Mountain View, CA 94043, USA. mdresser@alzus.jnj.com
Desai
D
D
Gidwani
S
S
Seftel
A D
AD
Modi
N B
NB
D000293:Adolescent; D000328:Adult; D001596:Benzylamines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D000068581:Tadalafil
D001596:Benzylamines; D002243:Carbolines; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068581:Tadalafil; D000068677:Sildenafil Citrate; C080598:dapoxetine