雷公藤内酯醇联用甘草次酸的药代动力学研究

Pharmacokinetics of Glycyrrhetinic Acid Combined with Triptolide in Rats in vivo

目的探讨甘草次酸对雷公藤内酯醇在大鼠体内的药代动力学行为的影响。方法将SD大鼠随机分为雷公藤内酯醇单独给药组和雷公藤内酯醇与甘草次酸联合给药组,分别通过尾静脉注射雷公藤内酯醇0.2mg/kg,采用液相色谱-质谱法(LC-MS),选择离子检测(SIM)的方式测定2组大鼠不同时间血浆中的雷公藤内酯醇浓度,比较2组在大鼠体内的药代动力学行为。结果在0.2~250ng/mL质量浓度范围内,血浆中雷公藤内酯醇线性良好。定量下限为0.2ng/mL,日内和日间精密度RSD均<12.0%,准确度为90%~105%,绝对回收率>80%,基质效应>90%,血浆样品的稳定性良好。药代动力学数据显示,联合给药组的最大血药浓度(c_(max))、消除半衰期(t_(1/2))、平均滞留时间(MRT_(0~180min))、血药浓度-时间曲线下面积(AUC_(0~180min))分别是单独给药组的0.75,2.51,1.15及1.39倍,其中t_(1/2)、MRT_(0~180min)在2组间的差别有统计学意义(P<0.05)。结论甘草次酸与雷公藤内酯醇联用可降低雷公藤内酯醇的峰浓度,延长其体内滞留时间,从而提高其大鼠体内的生物利用度;该测定方法简便、效率高、重复性好,符合生物样品分析的基本要求。

Objective To investigate the pharmacokinetics of glycyrrhetinic acid combined with triptolide（TPL）in SD rats. Methods The SD rats were divided into single and combined ad ministration groups. The combined group was injected with triptolide and glycyrrhetinic acid（w/w=1∶1）at the dose of 0.2 mg/kg,while the single group was injected only with triptolide at the dose of 0.2 mg/kg.The concentration of triptolide in plasma in vivo was deter mined by LC-MS method. Results The deter mination methods with good precision and stability were suitable for the assay of triptolide in biological samples. The linear range of 0.2～200 ng/mL and quantification of 0.2 ng/mL were established. The mean absolute recovery was more than 85% . The relative standard deviation（RSD）of intra-day and inter-day were all less than 12% . The results showed that the c_（max）,t1/2,MRT0～180 min,AUC0～180 min of combined ad ministration group were 0.75,2.51,1.15,1.39 times of that of the single ad ministration group in the plasma respectively. Between the two groups,the t1/2,MRT0～180 min were statistically significant.Conclusion The method was proved to be convenient,sensitive,rapid and suitable for pharmacokinetics study. Glycyrrhetinic acid can extend the residence time of TPLin vivo and prolong the circulation time of TPLin vivo remarkable.