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目的 估测天麻钩藤饮、镇肝熄风汤、建瓴汤 3个平肝熄风代表方的毒效动力学参数。方法 将药物动力学中多点动态测定的原理与动物死亡率测定药物蓄积性的方法结合起来 ,即用多组动物 ,按不同的间隔时间给药 ,求出不同时相下的体存百分率以观察方药中毒性成分在体内的动态变化 ,进而求出相关药代动力学参数。结果 3方均属二房室模型分布 ,基本上按一级动力学消除。天麻钩藤饮、镇肝熄风汤、建瓴汤的半数致死量分别为 5 8.0 4g/kg、10 0 .2 2g/kg、98.74g/kg ;表观消除速率常数为 0 .0 18、0 .0 11、0 .0 2 1;表观消除半衰期为 39.13h、6 1.49h与 32 .40h ;表观分布速率常数分别为 0 .0 92、0 .0 6 9、0 .144 ;表观分布半衰期为 7.5 2h、10 .0 8h与 4.80h ,3方毒性作用对性别影响无明显差异。结论 3方似具有明显的毒性作用 ,这可能与毒效法测定时的腹腔给药途径有关。
Objective To estimate the toxic effect kinetic parameters of Tianma Gouteng Yin, Zhengan Xifeng Decoction and Jianye Decoction. Methods The principle of multi-point dynamic measurement in pharmacokinetics was combined with the method of animal mortality determination of drug accumulation, ie, multiple groups of animals were dosed at different intervals to determine the percent of body weight at different phases. Observe the dynamic changes of the toxic components in prescriptions and obtain the relevant pharmacokinetic parameters. Results All three parties were distributed in a two-compartment model and basically eliminated by first-order kinetics. The median lethal doses of Tianma Gouteng Yin, Zhengan Xifeng Decoction and Jianye Decoction were 5 8.0 4g/kg, 10 0.22 g/kg, and 98.74 g/kg, respectively; the apparent elimination rate constant was 0.01. The average elimination half-lives were 39.13h, 6 1.49h and 32.40h, and the apparent distribution rate constants were 0. 0 92, 0. 0 6 9 and 0. 144, respectively. The observed distribution half-lives were 7.5 2 h, 10.08 h, and 4.80 h, and there was no significant difference in gender effects of the 3-party toxicity. Conclusions The three-party analogs have obvious toxic effects, which may be related to the intraperitoneal route of administration at the time of toxicity assay.