五味子甲素对CYP3A活性的影响及其体内外相关性研究  

Study on the Effects of Schisandra A on CYP3A Activity and the Correlation between the Results in vivo and in vitro

作　　者：辛华雯[1] 苏明威[1] 李维亮[1] 吴笑春[1] 李罄[1] 余爱荣[1] 姚国庆[1] 

机构地区：[1]广州军区武汉总医院临床药理科,武汉430070

出　　处：《中国药师》2011年第1期9-12,共4页China Pharmacist

基　　金：湖北省卫生厅科研基金资助(编号:2007JX3B38)

摘　　要：目的:通过"探针"法探讨五味子甲素体内、外对大鼠肝微粒体CYP3A活性的影响及其相关性。方法:选取咪达唑仑作为CYP3A探针,用高效液相色谱法测定五味子甲素体外孵育给药和体内灌胃给药后大鼠肝微粒体酶CYP3A活性,通过药动学参数K_m确定其体内、外作用的相关性。结果:体外试验结果表明,五味子甲素非竞争性抑制咪达唑仑的代谢,其K_i为5.5μmol·L^(-1),体内试验亦证实了五味子甲素能显著抑制肝微粒体CYP3A酶活性(P<0.01)并呈剂量依赖性,其体内给药的K_i值为30.67 mg·kg^(-1)。体内外K_m值十分接近。结论:五味子甲素在体内和体外均可非竞争性抑制大鼠肝微粒体酶CYP3A活性,其对CYP3A影响的体内、体外结果具有良好的相关性。Objective： To investigate the effects and correlation between in vivo and in vitro of schisandra A （SchA） on CYP3A activity in rat microsome by ＂probe＂ method. Method： Midazolam was used as a probe drug of CYP3A. High performance liquid chromatography was employed to determine CYP3A activity in rat microsome after SchA incubation in vitro and oral administration in rat. The correlation between the results in vitro and in vivo was evaluated by Km value. Result： The results in vitro indicated that SchA could noncompetitively inhibit the metabolism of midazolam and the Ki value was 5.5 μmol·L^-1. The results in vivo showed that SchA could significantly inhibit CYP3A activity in rat microsome with dose dependence （P 〈 0. 01 ） and the Ki value was 30. 67 mg·kg^-1. The Km value in vitro was similar to that in vivo. Conclusion： SchA could noncompetitively inhibit CYP3A activity in rat microsome both in vitro and in vivo. The results in vitro and in vivo have good correlation.

关 键 词：CYP3A 五味子甲素 咪达唑仑 高效液相色谱法 

分 类 号：R285.5[医药卫生—中药学]