摘要
目的:研究甘草对雷公藤甲素药代动力学及组织分布与排泄的影响,从药物相互作用影响代谢角度阐明甘草对雷公藤甲素的减毒作用机制。方法:采用平行对照试验,将SD大鼠随机分为单独和联合给药组,联合给药组提前灌服甘草后,尾静脉注射雷公藤甲素,采用LC-MS/MS法在离子对监测(MRM)模式下测定雷公藤甲素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甲素浓度,比较单独和联合给药后雷公藤甲素药代动力学及组织分布与排泄的差异。结果:雷公藤甲素在测定范围内均呈良好线性关系(r>0.99),日内和日间精密度均好(RSD<10%),血浆中提取回收率均大于80%,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后的药代动力学参数及组织分布与排泄均有明显差异。与单独给药组比,联合给药组的AUC与Cmax减小约1倍,而清除率(CL)增大约1倍,但两者的半衰期(t1/2z)差别不大;联合给药组组织分布浓度均较单独给药组平缓;单独和联合给药组雷公藤甲素均主要从尿液中排出,联合给药组由尿液中排泄更多,而单独给药组则从粪便中排泄更多,联合给药组尿液和粪便排出总量比单独给药组多将近1倍。结论:甘草对雷公藤甲素药代动力学及组织分布与排泄均有显著影响,甘草可加速雷公藤甲素体内代谢与排泄,平缓组织分布浓度,这可能是甘草对雷公藤甲素的减毒作用机制之一。
Objective：To study the effect of Glycyrrhiza uralensis on metabolism,distribution and excretion of triptolide in rat and disclose the attenuation mechanism of Glycyrrhiza uralensis on triptolide.Methods：The SD rats were divided into single and combined administration groups.The combined group was injected with triptolide after orally treated with extracts of Glycyrrhiza uralensis,while the single group was injected only with triptolide.The concentration of triptolide in plasma,tissue and excreta of rats were determinated by LC-MS/MS method to compare the difference of metabolism,distribution and excretion of triptolide under two administration models.Results：The determination methods with good precision and stability were suitable for the assay of triptolide in biological samples.The difference of metabolism,distribution and excretion of triptolide under single and combined administration models were significant.AUC and Cmax of triptolide under combined administration model were decreasing,while CL was increasing and t1/2z was maintained compared with single administration model.The concentration of triptolide in tissue under combined administration model was decreasing,while excretion of triptolide was accelerated compared with single administration model.Conclusion：Glycyrrhiza uralensis can decrease the concentration of triptolide in tissue and accelerate the excretion of triptolide in rats.It may be one of the attenuation mechanisms of Glycyrrhiza uralensis on triptolide.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2010年第9期1664-1671,共8页
Chinese Journal of Pharmaceutical Analysis
基金
江西省教育厅科技项目(GJJ08332)
关键词
甘草
雷公藤甲素
药代动力学
组织分布
排泄
Glycyrrhiza uralensis
triptolide
metabolism
distribution
excretion
