Dose-dependent pharmacokinetics and first-pass effects of mirodenafil, a new erectogenic, in rats.
The pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous (5, 10, 20 and 50 mg/kg) and oral (10, 20 and 50 mg/kg) administration of mirodenafil, and the first-pass effect of mirodenafil after intravenous, oral, intraportal, intragastric and intraduodenal (20 mg/kg) administration of mirodenafil were evaluated in rats. The pharmacokinetics of mirodenafil and SK3541 were dose-dependent after both intravenous and oral administration of mirodenafil due to the saturable hepatic metabolism of mirodenafil. After oral administration of mirodenafil, approximately 2.59% of the oral dose was not absorbed, the F value was approximately 29.4%, and the hepatic and gastrointestinal first-pass effects of mirodenafil were approximately 21.4% and 54.3% of the oral dose, respectively. The low F value of mirodenafil in rats was mainly due to considerable hepatic and gastrointestinal first-pass effects in rats. The equilibrium plasma-to-blood cell partition ratios of mirodenafil were independent of the initial blood mirodenafil concentrations of 1-10 microg/ml; the mean values were 1.08-1.21. The plasma binding values of mirodenafil to rat plasma was 87.8%.
Choi
Young H
YH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Lee
Young S
YS
Bae
Soo H
SH
Kim
Tae K
TK
Lee
Bong-Y
BY
Lee
Myung G
MG
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D058986:Phosphodiesterase 5 Inhibitors; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D058986:Phosphodiesterase 5 Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; C528396:mirodenafil