参麦注射液对大鼠细胞色素P450酶亚型活性的影响

Effect of Shenmai Iniection on isoforms of cytochrome P450 enzymes in rats

目的用Cocktail探针药物法研究参麦注射液对大鼠细胞色素P450酶（CYP450）6种亚型活性的影响。方法将SD大鼠随机分组,实验组ip给予参麦注射液（10 m L/kg）,对照组ip给予等量生理盐水,诱导7 d,分别以非那西丁、安非他酮、甲苯磺丁脲、奥美拉唑、美托洛尔和咪达唑仑作为CYP1A2、CYP2B1、CYP2C9、CYP2C19、CYP2D6和CYP3A4的探针药物。UPLC-MS/MS法检测大鼠血浆中探针药物的血药浓度,采用DAS3.0软件估算药动学参数。结果与对照组相比,非那西丁、安非他酮和奥美拉唑的AUC0^∞、CL和Cmax显著降低（P〈0.05）,甲苯磺丁脲、美托洛尔和咪达唑仑的AUC0^∞、CL和Cmax无显著性差异。结论参麦注射液对大鼠CYP1A2、CYP2B1和CYP2C19亚型的活性有明显的抑制作用,而对CYP2C9、CYP2D6和CYP3A4亚型的活性无显著性影响。

Objective To investigate the effects of Shenmai Injection（SMI） on activities of six isoforms of cytochrome P450（CYP450） by Cocktail probe drugs in rats. Methods SD rats were randomly divided into SM group and blank control group, which were given SMI（10 m L/kg） or normal saline for 7 d. Phenacetin, bupropion, tolbutamide, omeprazole, metoprolol, and midazolam were used as probe drugs for CYP1A2, CYP2B1, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The UPLC-MS/MS method was used to determine the concentration of probe drugs in rat plasma, and the pharmacokinetic parameters were estimated by DAS3.0.Results Compared with the blank control group, AUC0~∞, CL, and Cmax of phenacetin, bupropion, and omeprazole were significantly decreased（P 〈 0.05）. However, no significant difference of plasma concentration and pharmacokinetics for tolbutamide,metoprolol, and midazolam was shown between SMI group and the blank control group. Conclusion SMI can inhibit CYPl A2,CYP2B1, and CYP2C19 activities significantly, but has no effect on the activities of CYP2C9, CYP2D6, and CYP3A4.