两种方法测定麻黄汤体内过程的比较

Comparison of Mahuang Tang Dispositions in Rodents by Two Methods

目的:以毒理效应法和药理效应法分别测定麻黄汤的体内过程,比较两法的异同。方法:毒理效应法以小鼠死亡率为指标,不同时间先后2次ip麻黄汤19.69 g·kg-1测定其表观药动学参数;药理效应法采用大鼠酵母致热模型,以解热效应为指标,ig给予麻黄汤11.2 g·kg-1测定表观药动学参数。DAS 2.1.1程序拟合表观药动学数据并计算参数。结果:毒理效应法测得麻黄汤体内呈二室开放模型,主要药动学参数t1/2β=9.36 h,AUC=46.80 g·kg-1.h,CL=0.32(g·kg-1)/(h·g·kg-1)。药理效应法测得麻黄汤体内呈一室模型,主要药动学参数t1/2=4.15 h,AUC=55.01 g·kg-1.h,CL=0.27(g·kg-1)/(h·g·kg-1)。结论:2法测得参数存在一定差异,毒理半衰期长于效应半衰期。生物效应法可用于探讨中药方剂体内过程,但所得参数意义及数值均与经典药动学有差异。

Objective：To investigate the dispositions of Mahuang Tang in rodents by the drug cumulative method and pharmacological effect method and to make a comparison.Method：Taking mortality as the index,mice were injected ip with 19.69 g·kg-1 Mahuang Tang twice at different time points,and the disposition of Mahuang Tang was determined by the drug cumulative method.Taking antipyretic effects as the index,rats with yeastinduced fever were administered 11.2 g·kg-1 ig of Mahuang Tang,the disposition was determined by the pharmacological effect method.Pharmacokinetic parameters were determined using DAS software version 2.1.1.Result：The drug cumulative method showed a two-compartment model to describe the disposition,the apparent pharmacokinetic parameters were t1/2β=9.36 h,AUC=46.80 g·kg-1·h,CL=0.32（g·kg-1）/（h·g· kg-1）.The pharmacological effect method applied a one-compartment model to describe the disposition,the apparent pharmacokinetic parameters were t1/2=4.15 h,AUC=55.01 g·kg-1·h,CL=0.27（g·kg-1）/（h·g· kg-1）.Conclusion：The pharmacokinetic parameters from two methods are quite different.The drug cumulative method results in a longer elimination half-hour than that of the pharmacological effect method.The biological effect method can be applied to investigate the disposition of traditional medical formulae,predicting pharmacokinetic parameters with different values and meaning apart from the classic pharmacokinetic method.