Cocktail探针药物法评价半夏泻心汤及不同配伍组对CYP450酶活性的影响

目的:采用Cocktail探针药物法研究半夏泻心汤及不同配伍组对大鼠肝细胞色素P450酶活性的影响.方法:大鼠连续7d灌胃半夏泻心汤全方组,甘补组,苦降组和辛组的煎煮液(15 mL·kg-1)后尾静脉注射Cocktail探针药物咖啡因(CYP1A2)、甲苯磺丁脲(CYP2C6)、氯唑沙宗(CYP2E1)、咪达唑仑(CYP3A1/2).建立LC-MS/MS法测定大鼠血浆中4种探针药物的浓度,DAS 2.0软件计算其药动学参数.结果:与空白组相比,全方组中甲苯磺丁脲的AUC0-24h值明显增大,CL显著减小,说明全方组对大鼠体内CYP2C6起抑制作用,而氯唑沙宗的AUC明显减少,CL增大,说明对CYP2E1起诱导作用；而对CYP1A2,3A1/2无显著性差异.同理,辛开组仅对CYP2C6起抑制作用,对其他的亚型酶无显著性差异；苦降组对CYP1A2,CYP2C6具有显著抑制作用,对CYP2E1有诱导作用,而对CYP3A1/2无显著性差异；甘补组对CYP1A2,CYP2E1有诱导作用,抑制CYP2C6,而对CYP3A1/2亦无显著性差异.结论:半夏泻心汤及不同配伍组对肝脏CYP450酶的活性影响不同,为阐明半夏泻心汤组方配伍的规律用以推测其在联合用药中可能发生的药物相互作用,指导临床合理用药.

Effects of Components in Banxia Xiexin Decoction Prescription Compatibility on Activities of Cytochrome P450 in vivo

Objective: To evaluate the effects of Banxia Xiexin decocotion on P450 activities by Cocktail probe drugs in rats, provide a reference for clinical medication. Method: Four probe drugs (caffeine,tolbutamide,chlorzoxazone,midazolam) were simultaneously injected to rats after gavaged decoctions of Banxia Xiexin and its compatibilities for 7 days. The plasma concentrations of the four probes were measured by LC-MS-MS and their corresponding pharmacokinetic parameters were calculated. Result: Compared with the control group, the Banxia Xiexin decoction inhibited the espression of CYP2C6, and activated the expression of CYP2E1,but there were no differences on CYP3A1/2, CYP1A2;pungent-swelling group only inhibitied CYP2C6; bitter-descending group inhibitied of CYP1A2 and CYP2C6 expressi on, activatied CYP2E1,CYP3A1/2 no significant difference; sweet-invigorating group inductied the activity of CYP1A2, CYP2E1, inhibition of CYP2C6,and CYP3A1/2 there is no significant difference. Conclusion: Banxia Xiexin decoction and different conbinations have different functions on liver CYP450 enzyme activity.In clinic,We must be aware of possible drug-drug interactions when Banxia Xiexin decoction was used with other drugs.