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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 study the effect of Shenmai injection on the activities of six cytochrome P450 enzymes (CYP450) subtypes by using Cocktail probe drug method. Methods SD rats were randomly divided into experimental group (ip) given Shenmai injection (10 m L / kg) and control group (ip) given normal saline for 7 days. The rats were treated with phenacetin, bupropion, Sulfobutamide, omeprazole, metoprolol and midazolam as probes for CYP1A2, CYP2B1, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Plasma concentrations of probe drugs in plasma were detected by UPLC-MS / MS. Pharmacokinetic parameters were estimated by DAS 3.0 software. Results Compared with the control group, the values of AUC0 ~ ∞, CL and Cmax of phenacetin, bupropion and omeprazole were significantly decreased (P <0.05), while those of tolbutamide, metoprolol and midazolam Lun AUC0 ~ ∞, CL and Cmax no significant difference. Conclusion Shenmai injection significantly inhibits the activity of CYP1A2, CYP2B1 and CYP2C19 subtypes in rats, while has no significant effect on the CYP2C9, CYP2D6 and CYP3A4 subtypes.