20味中成药对5个人肝微粒体酶活性的影响  

Effects of 20 Chinese patent medicines on the catalytic activities of five main cytochrome P450s of human liver microsome

作　　者：徐斌[1] 赵刚[2] 位华[2] 钱小峰[2] 李静娴[2] 徐文[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院,上海200025 [2]中国人民解放军第二军医大学长征医院,上海200003

出　　处：《药学实践杂志》2009年第5期353-356,共4页Journal of Pharmaceutical Practice

基　　金："重大新药创制"科技重大专项课题资助。基金名称:中药5类新药甘西鼠尾总酚酸片临床前研究(2009ZX09102-134);中药药效物质基础及物质资源库研究关键技术(2009ZX09502-013)

摘　　要：目的:考察六神丸等20个常用中成药对CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4这5个人肝微粒体中主要的药物代谢酶的活性是否有影响。方法:采用人肝微粒体孵育法,分别采用非那西丁、甲苯磺丁脲、美芬妥因、氢溴酸右美沙芬和咪达唑仑作为5个酶的探针药物,采用液相色谱-质谱联用法测定了探针药物代谢产物的浓度,比较分别加入待测药物和空白缓冲液时代谢产物的初始生成速度。结果:六神丸对CYP1A2有明显抑制作用,IC50为28.75μg/mL;肝苏颗粒对CYP2C19有明显抑制作用,IC50为29.80μg/mL;丹参片对CYP1A2有明显抑制作用,IC50为48.55μg/mL;贝羚胶囊对CYP1A2有明显抑制作用,IC50为17.45μg/mL;复方夏天无片对CYP2D6有明显抑制作用,IC50为40.26μg/mL;丹参酮胶囊对CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4均有明显抑制作用,IC50分别为7.04、13.97、55.77、33.90μg/mL和34.57μg/mL;通风定胶囊对CYP2D6有明显抑制作用,IC50为37.56μg/mL结论:所测定的多数中成药对药物代谢酶有明显的抑制作用,这些药物与药物代谢酶的底物药物联用发生药物相互作用的可能性较大,临床联合用药须谨慎。Objective ：The effects of the 20 Chinese Patent Medicines on the catalytic activities of five main drug metabolism enzymes of human liver microsome, CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP 3A4, were assessed. Methods： Human liver microsome incubation experiment was carried out to assay the injection on the catalytic activities of the enzymes. Phenacetin, tolbutamide, S-mephenytoin, dextrometborphane and midazolam were used as the substrates of the enzymes. After the incubation, the five metabolites of the substrates were quantified by HPLC-MS/MS method. The inhibition was calculated by comparing the formation velocities of metabolites with or without test drug. Results ： Liu Shen Pill showed obvious inhibitory effect on CYP1A2 with an IC50 of 28.75 μg/mL; Gan Su Granule showed obvious inhibitory effect on CYP2C19 with an IC50 of 29.80 μg/mL; Dan Shen Tablet showed obvious inhibitory effect on CYP1 A2 with an IC50 of 48.55 μg/mL; Bei Ling Capsule showed obvious inhibitory effect on CYP1 A2 with an IC50 of 17.45 μg/mL; Xia Tian Wu Compound Tablet showed obvious inhibitory effect on CYP2D6 with an ICs0 of 40.26 μg/mL; Tanshinone Capsule showed obvious inhibitory effects on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 with IC50s of 7.04, 13.97, 55.77, 33.90 and 34.57 μg/mL. Tong Feng Ding Capsule showed obvious inhibitory effect on CYP2D6 with an IC50 of 37.56 μg/ mL. Conclusion ： Most test drugs showed obvious inhibitory effect on the catalytic activities of drug metabolism enzymes. The result indicated that Chinese Patent Medicine had the potential to induce drug - drug interactions and special attention should be paid when they are used in combined with other drugs.

关 键 词：中成药 人肝微粒体 药物代谢酶 抑制 

分 类 号：R286[医药卫生—中药学]