中国药理学通报Issue(9)：1298-1301,4.DOI:10.3969/j.issn.1001-1978.2014.09.024
灯盏乙素衍生物代谢性质的快速体外评价
Rapid pharmacokinetic characteristic evaluation of scutellarin derivatives in vitro
摘要
Abstract
Aim To study the pharmacokinetic char-acteristics of serial compounds that took the scutellarin and scutellarein as lead compounds by using the model of in vitro liver microsomes, and to screen compounds whose medicinal properties were superior to scutellarin and scutellarein. Methods The content of candidate compounds at different times by incubation system of rat liver microsome was determined using UPLC-MS/MS method. Candidate compounds that contained opti-mum T1/2 and CLint were screened. Enzyme kinetics and conversions of candidate compounds were com-pared with those of scutellarin and scutellarein. Re-sults The T1/2 and CLint were optimum of W11 com-pared with those of scutellarin and scutellarein; the Vmax, Km and CLint of compound W11 were (10.25 ±2.59 ) μmol · min-1 · g-1 , ( 4.64 ±0.24 ) μmol · L-1 and ( 2.29 ±0.23 ) L · min-1 · g-1; the Vmax , Km and CLint of scutellarin were (45.95±9.50) μmol · min-1 · g-1 , ( 10.19 ± 1.66 ) μmol · L-1 and (4.48±0.20) L·min-1 ·g-1; W11 might be me-tabolized into scutellarin and M1 ( a compound with mo-lecular weight of 577 after demethylating ) . Conclu-sion The pharmacokinetic properties of candidate compound W11 are better than those of scutellarin, and it could release scutellarin.关键词
灯盏乙素/灯盏乙素苷元/灯盏乙素衍生物/UPLC-MS/MS/肝微粒体/酶促动力学/代谢性质Key words
scutellarin/scutellarein/scutellarin de-rivatives/UPLC-MS/MS/liver microsomes/enzyme kinetics/pharmacokinetic characteristics分类
医药卫生引用本文复制引用
郑林,胡杰,曹旭,黄勇,董永喜,王永林..灯盏乙素衍生物代谢性质的快速体外评价[J].中国药理学通报,2014,(9):1298-1301,4.基金项目
国家自然科学基金资助项目( No 81060359) （ No 81060359）
贵州省中药现代化科技产业专项项目( No 黔科合中药字[2011]5029号) （ No 黔科合中药字[2011]5029号）
贵州省教育厅省长基金( No 黔省专合字[2011]50号) （ No 黔省专合字[2011]50号）
贵州省中药现代化科技产业研究开发专项( No 黔科合重G字[2013]4001) （ No 黔科合重G字[2013]4001）
