새로운 11β-HSD1 저해제인 KR-67500의 약물동태

초록

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 andanti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500as 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. Preclinicalpharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) tomale rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. Theseresults suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailabilityfor an oral therapeutic agent of diabetes and osteoporosis.

키워드