探针药物法评价苦参对大鼠细胞色素P450 2E1代谢活性的影响

目的以氯唑沙宗作为探针药物,研究苦参对大鼠细胞色素P450 2E1(CYP 2E1)体内代谢活性的影响。方法将Wistar大鼠随机分为对照组、苦参组、苯巴比妥阳性对照组。苦参组大鼠ig给予苦参颗粒(100 mg/kg)溶液,对照组ig给予等体积的生理盐水,阳性对照组ip苯巴比妥注射液50 mg/kg,各组均每日给药1次,连续5 d。第6天各组大鼠尾iv氯唑沙宗(5 mg/kg)溶液,于给药前及给药后不同时间点眼内眦静脉取血0.8 mL,HPLC法测定氯唑沙宗血药浓度。结果与对照组相比,苦参组给予苦参5 d后,氯唑沙宗的AUC和Cmax明显降低(P<0.05、0.01),CL明显升高(P<0.05);而苦参组的主要药动学参数与苯巴比妥组比较无显著差异(P>0.05)。结论苦参可明显诱导大鼠CYP 2E1的体内代谢活性,其作用强度与苯巴比妥相当。

Evaluation on effect of Sophora flavescens roots on metabolic activity of cytochrome P450 2E1 in rats by probe drug method

Objective To study the effect of Sophora flavescens roots on the metabolic activity of cytochrome P450 2E1(CYP 2E1) in rats with chlorzoxazone as probe drug.Methods The rats were randomly divided into three groups: control group,S.flavescens roots group,and phenobarbital group.S.flavescens roots granule and normal saline were ig administrated with a dose of 100 mg/kg once daily for 5 d to rats in S.flavescens roots and control groups,respectively.Sodium phenobarbital injection(50 mg/kg) was ip administered once daily for 5 d.On the day 6,the tails of all the rats in each group were iv injected with chlorzoxazone(5 mg/kg),then venous blood samples from rat’s eye canthus were collected at a set of time-points before and after the administration.The plasma concentration of chlorzoxazone was determined by HPLC.Results In S.flavescens roots group,AUC and Cmax of chlorzoxazone were significantly lower(P < 0.05,0.01) while CL was significantly higher(P < 0.05) than those of rats in the control group.There was no significant difference in the main pharmacokinetic parameters between S.flavescens roots and phenobarbital groups(P > 0.05).Conclusion S.flavescens roots could significantly induce the metabolic activity of CYP 2E1 in rats in vivo and the strength of the induction corresponds to that of phenobarbital.