用累积毒性原理评价口服中药体内过程

A method based on cumulative toxicity for evaluating pharmacokinetics of oral traditional Chinese medicine in animals

目的:改进动物急性累计死亡率法(ACD法) ,使其适于测算口服中药体内过程。方法:建立累次口服中药的药量 毒效关系模型以及相关的试验步骤,并用计算机模拟程序所提供的仿真模拟数据以及文献中真实试验数据进行方法学检验。结果:模拟试验结果表明,在LD95 2～LD5 2剂量范围内,试验值和理论值符合良好,方法稳定;对文献数据的重新计算得到:小鼠po马钱子粉符合口服给药开放一室模型,T1 2 (ka) =1.136h ,T1 2 (ke) =7.10 0h ,Tmax=3.5 76h。结论:改进ACD法可有效评价口服中药的体内过程。

AIM: To improve the acute cumulative death rates method (ACD method) in animal by oral administration. METHODS: A mathematic model was established to evaluate the dose-toxic effect relationship by twice oral administration and the experimental steps were improved too. The methodological quality was explored using the simulation data from computer program and the real experimental date from the reference paper. RESULTS: The results showed that the experimental data could be fitted to its theoretical data from LD_5/2 to LD_ 95/2. Concentration-time curve after po ordinary powder of Semen Strychni in mice were fitted to a one-compartment with T_ 1/2(ka)= 1.136 h,T_ 1/2(ke)= 7.100 h,and T_ max= 3.576 h. CONCLUSION: The improved ACD method can be used in the pharmacokinetics of TCM by oral administration.