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Pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous and oral administration of mirodenafil to streptozotocin-induced diabetes mellitus rats.

Abstract
The area under the curve (AUC) of mirodenafil after intravenous administration in diabetes mellitus induced by streptozotocin (DMIS) rats was significantly smaller (by 28.0 %) than the control value, and the AUC(SK3541)/AUC(mirodenafil) ratio was significantly greater (by 130 %) in DMIS rats. This may be explained by the significantly faster hepatic CL(int) of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values. The AUC of mirodenafil after oral administration was comparable between DMIS and control rats, possibly because of the comparable intestinal CL(int), which may be attributable to increased CYP1A2 expression and decreased CYP2D expression in the intestines of DMIS rats.
AuthorsY S Lee, Y H Choi, T K Kim, K H Ryu, B-Y Lee, M G Lee
JournalXenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 40 Issue 2 Pg. 129-37 (Feb 2010) ISSN: 1366-5928 [Electronic] England
PMID19929308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 2-(4-(3-(5-ethyl-7-n-propyl-3,5-dihydro-4H-pyrrolo(3,2-d)pyrimidin-4-onyl)-4-n-propoxyphenyl)sulfonylpiperazin-1-yl)ethyl hydrogen sulfate
  • N-dehydroxyethylmirodenafil
  • Pyrimidinones
  • Sulfonamides
  • mirodenafil
  • Streptozocin
Topics
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Diabetes Complications (drug therapy)
  • Diabetes Mellitus, Experimental (metabolism)
  • Erectile Dysfunction (drug therapy, etiology)
  • Infusions, Intravenous
  • Male
  • Pyrimidinones (administration & dosage, metabolism, pharmacokinetics)
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Sulfonamides (administration & dosage, metabolism, pharmacokinetics)

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