目的 用Cocktail探针药物法,研究雷公藤片对大鼠肝CYP450的影响.方法 分别以奥美拉唑和咪达唑仑作为CYP2C19和CYP3A4的探针药,将大鼠随机分为低剂量和高剂量两组,每日早晚灌胃雷公藤片,采用液质联用法测定连续使用雷公藤片前后大鼠血浆中相应的探针药物的浓度及其药代动力学参数.结果 连续灌胃10 d后,与用药前比较,奥美拉唑、咪达唑仑的血药浓度及其药代动力学参数有明显改变;低剂量组和高剂量组中咪达唑仑的AUC明显增加,CL/F明显降低,T(12)增大,Vd/F和Tmax变化不明显,高剂量组中Cmax有所增大;低剂量组中奥美拉唑的T(12)和Vd/F有所增大,高剂量组中AUC增加(P<0.05).结论 连续灌胃雷公藤片10 d后,雷公藤片对大鼠体内CYP3A4酶具有抑制作用;对CYP2C19酶具有一定的抑制作用.%Aim To evaluate the effects of Tripterygium wilfordii tablet on P450 activities by cocktail probe drugs in rats.Methods Two probe drugs ( omeprazole, midazolam )were simultaneously given to rats after low and high dosing of Tripterygium wilfordii tablets.The plasma concentrations of the two probes were measured by LC-MS and their corresponding pharmacokinetic parameters were calculated.Results There were some differences between omeprazole and midazolam in plasma concentrations and the corresponding pharmacokinetic parameters in rats after two dosing of Tripterygium wilfordii tablets administration.The AUC and T1/2 of midazolam increased significantly( P ＜0.05 ) and the CL/F decreased in rats after two dosing of Tripterygium wilfordii tablets for 10 consecutive days.No influences were observed on Tmax and Vd/F,but the Cmax of midazolam increased after high dosing of Tripterygium wilfordii tablets ; The T1/2 and Vd/F of omeprazole increased after low dosing of Tripterygium wilfordii tablets, and the AUC increased after high dosing of Tripterygium wilfordii tablets.Conclusion Tripterygium wilfordii tablets twice daily for 10 days can inhibit CYP3A4 activity significantly, and it may also have effect on CYP2C19.
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