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KMID : 0370220150590020059
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Yakhak Hoeji
2015 Volume.59 No. 2 p.59 ~ p.65
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Pharmacokinetic Characterization of KR-67500, a Novel 11β-HSD1 Inhibitor
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Im So-Hee
Ahn Jin-Hee
Kim Ki-Young
Bae Myung-Ae
Kim Sang-Kyum
Ahn Sung-Hoon
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Abstract
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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 11β-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.
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KEYWORD
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11β-HSD inhibitor, anti-diabetic agent, KR-67500, pharmacokinetics
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