中国药理学与毒理学杂志Issue(6)：924-930,7.DOI:10.3867/j.issn.1000-3002.2015.06.008
补骨脂素和异补骨脂素在大鼠和人肝微粒体的酶促动力学
Enzyme kinetics of psoralen and isopsoralen in rat and human liver microsomes
摘要
Abstract
OBJECTIVE To investigate and compare the enzyme kinetic characters of psoralen (PRN)and isopsoralen(IPRN)in rat and human liver microsomes. METHODS PRN and IPRN in liver microsomes incubates were determined using LC-MS/MS. The enzyme kinetic and metabolic stability of PRN and IPRN were investigated by employing the optimized rat and human liver microsomes incubations. The Vmax and Km values were calculated using the nonlinear regression method. RESULTS The quanti⁃tative method showed good linearity within the range of 0.1-50.0 μmol · L-1 and was suitable for the assay in biological samples. The in vitro elimination was linear with the substrate concentrations lower than 1 μmol,the protein concentration within 0.5 g · L-1,and the incubation time within 40 min. The t1/2 values of PRN and IPRN in rat and human liver microsomes were 74.5,95.0,74.5 and 173.3 min, respectively. The Vmax values of PRN in rat and human liver microsomes were(1.140±0.080)μmol·min-1·g-1 protein,(0.620±0.060)μmol·min-1·g-1 protein,while Km values of PRN in rat and human liver microsomes were (12.9 ± 0.3)μmol · L- 1,(7.4 ± 1.3)μmol · L- 1,respectively. The Vmax values of IPRN in rat and human liver microsomes were(0.251±0.012)and(0.103±0.014)μmol·min-1·g-1 protein,while Km values of IPRN in rat and human liver microsomes were (3.0 ± 0.4)μmol · L-1,(3.4 ± 0.7)μmol · L-1,respectively. CONCLUSION The enzyme kinetic characters and metabolic stability of PRN and IPRN show species and chemical structures related differences. Interestingly,the metabolic eliminations of PRN and IPRN are similar in rats. However,the metabolic elimination of IPRN in humans involved in CYP enzymes may be much slower than that of PRN.关键词
补骨脂素/异补骨脂素/肝微粒体/细胞色素P450酶系统/药代动力学Key words
psoralen/isopsoralen/liver microsomes/cytochrome P-450 enzyme system/pharma-cokinetics分类
药学引用本文复制引用
阳海鹰,钟玉环,陈琳,李桦,庄笑梅..补骨脂素和异补骨脂素在大鼠和人肝微粒体的酶促动力学[J].中国药理学与毒理学杂志,2015,(6):924-930,7.基金项目
国家科技重大专项（2012ZX09301003-001-009）；国家科技重大专项（2013ZX09J13103-01B）；国家科技重大专项（2014ZX09507001003）；国家科技重大专项（2014ZX09J14103-01A）@@@@The project supported by National Science and Technology Major Project （2012ZX09301003-001-009）；National Science and Technology Major Project（2013ZX09J13103-01B）；National Science and Technology Major Project（2014ZX09507001003）；and National Science and Technology Major Project （）
