总量统计矩法评价祛瘀清热颗粒中大黄酸与大黄酚在家兔体内的药代动力学特征

Total quantity statistical moment analysis on pharmacokinetics of rhein and chrysophanol after oral administration of Quyu Qingre granules in normal and acute blood stasis rabbits

为明确总量统计矩分析法的适用性,该文运用总量统计矩分析法获取祛瘀清热颗粒中大黄酸与大黄酚在家兔体内的整体药动学特征,同时获悉2个有效成分于生理和病理状态下在家兔体内的整体药动行为的差异。该文通过复制家兔血瘀模型,采用已建立的家兔血浆中大黄酸与大黄酚HPLC含量检测方法,测定灌胃祛瘀清热颗粒后正常与血瘀家兔体内2个成分的经时血药浓度,进一步采用总量统计矩分析法计算各总量药动学参数,比较2个成分在正常与血瘀家兔体内的整体药动学特征的差异。结果,血瘀组VRT t大于正常组,且具有显著性差异(P<0.05);血瘀组的AUC t,MRT t,t1/2t与V t参数值均大于正常组,而k t,CL t小于正常组;表明与正常家兔相比,大黄酸与大黄酚在血瘀家兔体内的总体入血量更大,释放和吸收更快,滞留时间更长,消除减慢。总量统计矩可整合大黄酸与大黄酚的药代动力学参数,能表达祛瘀清热颗粒中这2个有效成分整体的药代动力学行为。

This study aim to reveal the total pharmacokinetics of rhein and chrysophanol after oral administration of Quyu Qingre granules （QUQRG） in normal and acute blood stasis rabbits, to identify the pharmacokinetics differences between two groups of rabbits and to evaluate the applicability of the total statistical moment analysis. Based on the concentrations of rhein and chrysophanol in plasma determined by an established HPLC method, and the calculation of main total pharmacokinetic parameters, this study found that total pharmacokinetic parameters VRTt value of blood stasis group is lager than that of normal group and the difference is significant. Compared with normal group, total pharmacokinetic parameters AUCt , MRTt, t1/2t and Vt value of blood stasis group is lager, while the kt and CLt value is smaller. The findings indicated that the absorbed and released time of rhein and chrysophanol was accelerated and the total absorptive amount of these two compounds was increased in rabbits with acute blood stasis, compared with the normal rabbits. Total quantity statistical moment analysis can combine the pharmacokinetics of rhein and chrysophanol and express the pharmacokinetic behavior of these two compounds in QUQRG. The parameters in this paper can provide reference frames for the follow-up development of QUQRG.