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目的:研究甘草对雷公藤内酯酮药代动力学及组织分布与排泄的影响,为阐明甘草对雷公藤的减毒作用机制奠定基础。方法:采用对比试验,将SD大鼠随机分为雷公藤内酯酮单独给药组和雷公藤内酯酮与甘草联合给药组,联合给药组提前灌服甘草后,分别尾静脉注射雷公藤内酯酮1.4mg·kg-1,采用LC-MS/MS法在选择离子监测(SIM)模式下测定雷公藤内酯酮单独给药和与甘草联合给药后不同时间大鼠血浆、组织液和排泄物中的雷公藤内酯酮浓度,比较单独和联合给药后雷公藤内酯酮药代动力学及组织分布与排泄的差异。结果:雷公藤内酯酮在测定范围内均呈良好线性关系(r>0.99),日内和日间精密度RSD均小于15%,血浆中提取回收率均大于70%,各组织中提取回收率均大于60%,提取方法稳定可靠;单独给药和与甘草联合给药的药代动力学参数及组织分布与排泄均有明显差异。联合给药组的AUC与t1/2z明显小于单独给药组,而清除率(CL)则增大,说明联合给药组的代谢速度比单独给药组快;在组织分布中,单独给药组和联合给药组中雷公藤内酯酮均主要聚集于肺,联合给药组在组织中的分布浓度比单独给药组低;在排泄中,联合给药组中雷公藤内酯酮的排泄总量大于单独给药组约1倍。结论:甘草对雷公藤内酯酮药代动力学及组织分布与排泄均有显著影响,甘草可加速雷公藤内酯酮体内代谢与排泄,降低组织分布浓度,这可能与甘草降低雷公藤毒性有关。
OBJECTIVE: To study the effect of licorice on the pharmacokinetics and tissue distribution and excretion of triptolide, and lay the foundation for elucidating the attenuating mechanism of licorice on Tripterygium wilfordii. Methods: By comparative test, SD rats were randomly divided into triptolide alone group and triptolide combined with licorice group, combined with the group before the administration of licorice root, respectively, tail vein injection of triptolide Ketone 1.4mg · kg-1, determined by selective ion monitoring (SIM) mode by LC-MS / MS method in plasma, tissue fluid and excretion of rats after administration of triptolide alone and in combination with licorice at different times Of triptolide concentrations compared triptolide alone and in combination pharmacokinetics and tissue distribution and excretion differences. Results: Triptolide showed a good linearity (r> 0.99) in the determination range. The intra-day and inter-day RSD were less than 15%, and the recovery rates in plasma were more than 70%. The recovery rate More than 60%, the extraction method is stable and reliable; pharmacokinetic parameters and tissue distribution and excretion were significantly different between single administration and licorice administration. The AUC and t1 / 2z in the combination group were significantly smaller than those in the group administered alone, while the clearance (CL) increased, indicating that the combination group had a faster metabolism rate than the group administered alone. In the tissue distribution, the group administered alone Triptolide in the combination group and the combination group were mainly concentrated in the lung, the combined group in the distribution of concentrations in the tissue is lower than the single administration group; in excretion, the combined administration group triptolide excretion of total The amount is larger than that of the single administration group about 1 time. CONCLUSION: Licorice can significantly influence the pharmacokinetics and tissue distribution and excretion of triptolide. Glycyrrhizin can accelerate the metabolism and excretion of triptolide in vivo and decrease the tissue concentration, which may be related to the decrease of toxicity of TWH.