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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。
Objective To study the inhibitory effect of xingnaojing injection on five subtypes of human liver microsomal P450 enzyme in order to predict its potential metabolic drug interactions. Methods Human liver microsomes, xingnaojing injection and five probe substrates omeprazole, dextromethorphan, testosterone, chlorzoxazone and tolbutamide in nicotinamide adenine dinucleotide phosphate reductase Under the action of co-incubation at 37 ℃ water bath. The amount of metabolites produced by the probe substrate was determined by liquid chromatography-mass spectrometry (HPLC-MS), and the effects of XNX on the activity of these 5 enzyme subtypes were evaluated. Results In the in vitro incubation system of human liver microsome, Xingnaojing injection had a strong inhibitory effect on CYP2C19 with an IC 50 value of 0.36%, while its inhibitory effect on CYP2D6, CYP3A4, CYP2E1 and CYP2C9 was relatively Weak, the IC_ (50) values were 7.37%, 3.62%, 2.50% and 7.03% respectively. Conclusion Xingnaojing injection can inhibit CYP2C19 enzyme subtypes of activity, should pay attention to the potential metabolic drug interactions during clinical use.