以降酶法研究逍遥散在肝损伤大鼠的昼夜药动学

目的:研究昼夜给予逍遥散对肝损伤大鼠的药效动力学差异,为肝病患者服用逍遥散提供时间依据。方法:将大鼠sc 40%CCl4橄榄油溶液2 mL.kg-1每2 d 1次,首次sc 4 mL.kg-1,连续12 d,以AST降低量为药效指标,分别于早8点和晚8点单次ig逍遥散,通过测定降酶峰时、量效方程、时效方程,运用PKSolver 2.0统计距分析模块求算相关药动学和药效学参数。结果:逍遥散的降酶时-效曲线具有显著的双峰特性,其td,t1/2(ED),AUC,MRT分别为17.79 h,3.73 h,657.07 U.L-1.h-1,6.23 h(昼)和24.30 h,3.50 h,810.19 U.L-1.h-1,6.19 h(夜),昼夜td和AUC经统计学比较具有显著性意义。结论:逍遥散对肝损伤大鼠的药动学存在昼夜差异,在休息期末,活动期初(晚8点)给予逍遥散更为合理。

Enzyme-Reducing Action and Circadian Pharmacodynamics of Xiaoyao Powder on Liver Injury in Rats

Objective: To sutdy the enzyme-reducing action and pharmacodynamics of Xiaoyao powder on liver injury in rats in the morning and evening in order to provide chronomedication evidence for hepatopaths. Method: The liver injury rat model was developed by subcutaneous injection of forty percent carbon tetrachloride every two days.With the decrease of aspartate amino transferase as the parameter,the pharmacodynamics in the morning and evening of Xiaoyao powder was studied.The apparent parameters of pharmacodynamics were estimated based on the time-effect curve by PKSolver 2.0. Result: The time-effect curve of Xiaoyao powder shows characteristics of double peaks and can be described by statistical moment.The main pharmacodynamic parameters are as follows: t_d=17.79h(day),24.30h(night),t_1/2(ED)=3.73h(day),3.50h(night),AUC=657.07U ·L^-1 ·h^-1(day),810.19U ·L^-1 ·h^-1(night),MRT=6.23h(day),6.19h (night), respectively. Conclusion: Significant circadian rhythm of pharmacodynamics was found in rats when Xiaoyao powder was given at different times of the day.The findings suggest that the hepatic protection effect for liver injury of Xiaoyao powder in rats is better when given at the end of rest phase than other time session.