SM-1对人肝微粒体细胞色素P450亚型酶的抑制作用

摘要

Aim To investigate the effect of SM-1 on seven main cytochrome P450(CYP450)in human liver microsomes.Methods Substrate or SM-1 was incubated with human liver microsomes for 30 min in vitro,and divided into control group and experimental group.The effects of SM-1 on the main phase I metabolic enzymes in human liver microsomes was detected by HPLC.Phenacetin,bupropion,paclitaxel,tolbutamide,omeprazole,dextromethorphan,testosterone were investigated as probe drugs.Results Inhibition rate of SM-1 on the classical substrate of human liver microsomal CYP was 0.05％,3.37％,0.08％,2.07％,4.20％,-0.15％and 10.84％,respectively.Conclusions SM-1 may have inhibitory effect on CYP3A4.Attention should be paid to the interaction of clinical drug induced by CYP enzyme inhibition.%目的 观察SM-1对人肝细胞色素P450酶系统中7种亚型酶活性的影响.方法 在体外将一定浓度的底物或SM-1与人肝微粒体孵育30 min,分为对照组(底物)和实验组(底物和SM-1),以非那西丁、安非他酮、紫杉醇、甲苯磺丁脲、奥美拉唑、右美沙芬、睾酮为CYP探针底物,应用HPLC法检测各探针底物代谢量,计算抑制率,评价SM-1对人肝微粒体CYP1A2、2B6、2C8、2C9、2C19、2D6、3A4 酶的抑制活性.结果 SM-1对CYP1A2、2B6、2C8、2C9、2C19、2D6、3A4的抑制率分别是0.05％、3.37％、0.08％、2.07％、4.20％、-0.15％和10.84％.结论 SM-1对CYP3A4可能有抑制作用,临床用药时应注意因CYP酶抑制引起的药物相互作用.