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 mu g/ml; the mean values were 1.08-1.21. The plasma binding values of mirodenafil to rat plasma was 87.8%. Copyright (C) 2009 John Wiley & Sons, Ltd.