Dose-dependent pharmacokinetics and first-pass effects of mirodenafil, a new erectogenic, in rats

Young H. Choi, Young S. Lee, Soo H. Bae, Tae K. Kim, Bong Y. Lee, Myung G. Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 μg/ml; the mean values were 1.08-1.21. The plasma binding values of mirodenafil to rat plasma was 87.8%.

Original languageEnglish
Pages (from-to)305-317
Number of pages13
JournalBiopharmaceutics and Drug Disposition
Volume30
Issue number6
DOIs
StatePublished - 2009

Keywords

  • Dose-dependent pharmacokinetics
  • Flip-flop model
  • Hepatic and gastrointestinal first-pass effects
  • Mirodenafil
  • Rats
  • SK3541 and SK3544

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