새로운 11β-HSD1 저해제인 KR-67500의 약물동태

• 영문명: Pharmacokinetic Characterization of KR-67500, a Novel 11β-HSD1 Inhibitor
• 발행기관: 대한약학회
• 저자명: 임소희(So Hee Im) 안진희(Jin Hee Ahn) 김기영(Ki Young Kim) 배명애(Myung Ae Bae) 김상겸(Sang Kyum Kim) 안성훈(Sung-Hoon Ahn)
• 간행물 정보: 『약학회지』제59권 제2호 (2015년), 59~65쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2015.04.30

영문 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 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.

키워드

11β-HSD inhibitor anti-diabetic agent KR-67500 pharmacokinetics