混合探针法评价白香丹胶囊对大鼠体内CYP450酶活性的影响

Influence of Baixiangdan Capsules on Metabolic Activities of Cytochrome P450 Enzymes in Rats Evaluated by a Cocktail Method

目的:建立同时测定大鼠血浆中6种CYP450探针药物的方法,并采用Cocktail法研究白香丹胶囊对大鼠CYP450酶活性的影响。方法:选用茶碱(CYP1A2)、氯唑沙宗(CYP2E1)、甲苯磺丁脲(CYP2C6)、右美沙芬(CYP2D2)、奥美拉唑(CYP2D1)、咪达唑仑(CYP3A2)作为探针药物。大鼠随机分为对照组和给药组,给药组每天灌胃白香丹胶囊0.675 g·kg-1,对照组灌胃等量生理盐水,连续给药14 d。第15天均灌胃给予6个探针药物,于不同时间点眼眶取血,采用LC-MS/MS法测定各探针药物浓度,计算药动学参数并进行组间t检验。结果:与对照组相比,给药组茶碱(P<0.01)、氯唑沙宗(P<0.01)、甲苯磺丁脲(P<0.05)代谢显著加快;右美沙芬、奥美拉唑、咪达唑仑代谢无显著性差异。结论:白香丹胶囊对大鼠CYP1A2有中强诱导作用,对CYP2E1、CYP2C6有弱诱导作用。

Objective: To establish a method to detect six probe drugs in rat plasma and to study the influence of Baixiangdan Capsules on metabolic activities of cytochrome P450 enzymes in rats by a cocktail method. Methods: Theophylline(CYP1A2), chlorzoxazone(CYP2E1), tolbutamide(CYP2C6), extromethorphan(CYP2D2), omeprazole(CYP2D1) and midazolam(CYP3A2) were used as the probe drugs. The rats were randomly divided into two groups: control group and Baixiangdan group. Each rat of the Baixiangdan group was given oral Baixiangdan capsules at 0.675 g·kg-1per day for 14 days, while each rat of the control group was given equal volume of saline. Cocktail probe drugs were given on the 15 th day and plasma samples were taken at different time points as well as determined by LC-MS/MS. The pharmacokinetic parameters were calculated and t-test was operated. Results: Compared with the control group, the metabolism of theophylline(P<0.01), chlorzoxazone(P<0.01) and tolbutamide(P<0.05) in the Baixiangdan group were significantly accelerate, while the metabolism of dextromethorphan, omeprazole and midazolam had no significant difference. Conclusion: Baixiangdan capsules can moderately induce CYP1A2 and weakly induce CYP2E1 and CYP2C6 in rats.