疏血通注射液对大鼠细胞色素P450酶6种亚型活性的影响

目的用Cocktail探针药物法,研究疏血通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Wistar雄性大鼠随机分组,实验组给予疏血通注射液,空白组给予生理盐水,诱导7 d,分别以咖啡因、甲苯磺丁脲、奥美拉唑、美托洛尔、氯唑沙宗、氨苯砜作为CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP2E1、CYP3A1/2的探针药物。HPLC法检测探针药物的血药浓度,DAS软件估算药动学参数。结果与空白组相比,咖啡因和氨苯砜的t1/2、AUC0-t、AUC0-∞均显著增大,CL/F显著降低(P<0.05);氯唑沙宗的AUC0-t、AUC0-∞显著降低,CL/F显著增大(P<0.05);而甲苯磺丁脲、奥美拉唑、美托洛尔的药代动力学参数无显著性差异。结论疏血通注射液对大鼠CYP1A2、CYP3A1/2亚型的活性有抑制作用,能诱导CYP2E1亚型的活性,而对CYP2C9、CYP2C19和CYP2D6亚型的活性无显著影响。

Effects of Shuxuetong Injection on Activities of Six Isoforms of Cytochrome P450 in Rats

Objective To investigate the effects of Shuxuetong injection(SI) on activities of six isoforms of cy tochrome P450(CYP450) by Cocktail probe drugs in rats.Methods Male Wistar rats were randomly divided into SI group and blank control group,which were given SI or normal saline for 7 days.Caffeine,tolbutamide,omeprazole,metoprolol,chlorzoxazone and dapsone were used as probe drugs for CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP2E1 and CYP3A1/2,respectively.HPLC method was used to determine the concentrations of probe drugs in rat plasma.And pharmacokinetic parameters were estimated by DAS.Results Compared with the blank control group,t 1/2,AUC 0-t and AUC 0-∞ of caffeine and dapsone were significantly increased,and CL/F was significantly decreased(P<0.05).Moreover,in SI group,AUC 0-t and AUC 0-∞ of chlorzoxazone were lower,and CL/F was higher than those in the blank control group(P<0.05).However,No significant difference of plasma concentrations and pharmacokinetics for tolbutamide,omeprazole and metoprolol was shown between SI group and the blank control group.Conclusion Shuxuetong injection can inhibit CYP1A2 and CYP3A 1/2 activities significantly,and induce CYP2E1 activity significantly,but has no effect on the activities of CYP2C9,CYP2C19 and CYP2D6.