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http://dx.doi.org/10.17480/psk.2015.59.2.59

Pharmacokinetic Characterization of KR-67500, a Novel 11β-HSD1 Inhibitor  

Im, So Hee (College of Pharmacy, Chungnam National University)
Ahn, Jin Hee (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology)
Kim, Ki Young (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology)
Bae, Myung Ae (Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology)
Kim, Sang Kyum (College of Pharmacy, Chungnam National University)
Ahn, Sung-Hoon (College of Pharmacy, Kangwon National University)
Publication Information
YAKHAK HOEJI / v.59, no.2, 2015 , pp. 59-65 More about this Journal
Abstract
KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.
Keywords
$11{\beta}$-HSD inhibitor; anti-diabetic agent; KR-67500; pharmacokinetics;
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