醒脑静注射液对人肝微粒体P450酶5种亚型体外抑制作用

Inhibitory effect of Xingnaojing injections on five subtypes of human cytochrome P450 in vitro

目的研究醒脑静注射液对人肝微粒体P450酶5种亚型的体外抑制作用,以预测其潜在的代谢性药物相互作用。方法人肝微粒体、醒脑静注射液与5种探针底物奥美拉唑、右美沙芬、睾酮、氯唑沙宗和甲苯磺丁脲在烟酰胺腺嘌呤二核苷酸磷酸还原酶的作用下,于37℃水浴下共同孵育。通过液相色谱-质谱分析方法,测定探针底物的代谢产物生成量,评价醒脑静注射液对这5种酶亚型活性的影响。结果在人肝微粒体体外孵育反应体系中,醒脑静注射液对CYP2C19有较强的抑制作用,其IC_(50)值为0.36%;而对CYP2D6、CYP3A4、CYP2E1和CYP2C9的抑制作用相对较弱,其IC_(50)值为分别为7.37%、3.62%、2.50%和7.03%。结论醒脑静注射液可抑制CYP2C19酶亚型的活性,在临床使用过程中应注意潜在的代谢性药物相互作用。

AIM To investigate inhibitory effect of Xingnaojing injection on the activities of five isoenzyme of human liver microsomes cytochrome P450 in vitro for predicting potential metabolism-based drug- drug interactions in clinic. METHODS Human liver microsomes and five probes including omeprazole, dextromethorphan, testosterone, chlorzoxazone and tolbutamide were incubated with the injection at 37 ~C in presence of NADPH. The concentrations of produced metabolites in the reaction were determined by LC-MS/MS. RESULTS Xingnaojing injection stongly inhibited CYP2C19 with an IC50 value of 0.36%, and weekly inhibited CYP2D6, CYP3A4, CYP2E1 and CYP2C9 activities with IC50 values of 7.37%, 3.62%, 2.50% and 7.03%, respectively. CONCLUSION Xingnaojing injection could inhibit on the activity of CYP2C19 isoenzyme. It suggests that caution should be paid to the potential drug-drug interactions in clinic.