细辛脑注射液对人肝微粒体P450酶的体外抑制作用  

Inhibitory Effect of Asarone Injection on P450 Enzyme Activities in Vitro

作　　者：叶林虎 孔令提[2] 贺梅 王宇奇 何应军 陈翠 

机构地区：[1]毕节市第一人民医院药剂科,贵州毕节551700 [2]蚌埠医学院第一附属医院药剂科,安徽蚌埠23300

出　　处：《中国药物警戒》2016年第12期705-707,711,共4页Chinese Journal of Pharmacovigilance

基　　金：贵州省科学技术基金项目(黔科合J字[2015]2004号);毕节市科技局资助项目(毕科合[2015]62号);贵州省卫生计生委科学技术基金项目(2015-1-074)

摘　　要：目的研究细辛脑注射液对人肝微粒体P450酶5种亚型活性的体外抑制作用,以预测其潜在的代谢性药物相互作用。方法人肝微粒体、细辛脑注射液与5种探针底物在NADPH还原酶的作用下,于37℃水浴下共同孵育。采用液质联用技术,分析各探针底物代谢产物的变化情况,评价细辛脑注射液对这5种酶亚型活性的影响。结果细辛脑注射液对CYP2D6、CYP3A4、CYP2C19、CYP2E1和CYP2C9抑制的IC50值分别为26.44、36.16、52.00、102.40和55.86μg·m L-1。结论细辛脑注射液对5种酶亚型的活性均有一定的抑制作用,在临床使用过程中可能发生潜在药物相互作用,应注意避免不必要的联合用药。objective To evaluate inhibitory effect of asarone injection on the activities of human liver microsomes cytochrome P450（CYP） enzymes including CYP2D6, CYP3A4, CYP2C19, CYP2E1 and CYP2C9 in vitro for predicting potential metabolic drug interactions. Methods Human liver microsomes and five probes were incubated with different concentrations of asarone injection at 37℃ in presence of NADPH. The concentrations of produced metabolites in the reaction solution were determined by an LC-MS/MS method, and compared for evaluating the activity of isoenzymes. Results The inhibitory effects of asarone injection on the isoenzymes were mainly dependent on the concentrations. The injection inhibited CYP2D6,CYP3A4,CYP2C19,CYP2E1 and CYP2C9 activities with IC50 values of 26.44, 36.16, 52.00, 102.40 and 55.86 μg·m L-1, respectively. Conclusion Asarone injection was found to have inhibitory effect on P450 activities. Extreme caution should be taken regarding the use of this injection to avoid the potential risks of metabolic drug interactions with conventional drugs in the clinic.

关 键 词：细辛脑注射液 细胞色素P450酶 抑制作用 药物相互作用 

分 类 号：R969[医药卫生—药理学]