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

Abstract

1. 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.

2. 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.

Keywords::

• Pharmacokinetics
• mirodenafil
• SK3541
• and SK3544
• diabetes mellitus induced by streptozotocin
• hepatic and intestinal CYP isozymes
• rats

Acknowledgements

Declaration of interest

This work was supported in part by the contract ‘Pharmacokinetics of mirodenafil’ from SK Chemicals, Seoul, South Korea.