Authors: JongShik Park MinSun Kim Jin Sook Song Sung Heum Choi Byung Hoi Lee Jaechun Woo Jin Hee Ahn Myung Ae Bae SungHoon Ahn
Publish Date: 2011/12/31
Volume: 34, Issue: 12, Pages: 2051-2058
Abstract
The pharmacokinetics of a novel peroxisome proliferatoractivated receptorγ agonist KR62980 were characterized in vitro with respect to liver metabolic stability cell permeability and plasma protein binding and in vivo using SpragueDawley rats and ICR mice The metabolic halflife of 01–10 μM KR62980 was 115–152 min in rat liver microsomes and 258–288 min in human liver microsomes KR62980 showed high permeability across MDCK cell monolayers with apparent permeability coefficients of 204 × 10−6 to 308 × 10−6 cm/sec The plasma protein binding rate of KR62980 was 894 and most was bound to serum albumin After intravenous administration of KR62980 2 mg/kg the systemic clearance was 250 L/h/kg and the volume of distribution at steadystate was 916 L/kg The bioavailability after oral administration was approximately 609 The dosenormalized AUC values were 050 ± 009 041 ± 020 and 062 ± 008 h·μg/mL after oral administration of 2 5 and 10 mg/kg KR62980 respectively showing no dosedependency The in vivo pharmacokinetic parameters in ICR mice were also dose independent These data suggest that KR62980 is not significantly dose dependent in rats or mice although it may disappear rapidly from the systemic circulation via metabolism in the liver
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