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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。
OBJECTIVE: To study the pharmacokinetics of Xiaoyao San on rats with liver injury by day and night, and to provide a time basis for patients with liver disease to take Xiaoyaosan. Methods: The rat sc 40% CCl4 olive oil solution 2 mL.kg-1 once every 2 days, the first sc 4 mL.kg-1, for 12 consecutive days, with AST decreased as a pharmacodynamic indicator, respectively, as early as 8 Point and 8 pm single ig Xiaoyao San, by measuring the peak of the enzyme peak, the dose-effect equation, aging equation, the use of PKSolver 2.0 statistical distance analysis module to calculate the relevant pharmacokinetic and pharmacodynamic parameters. Results: Xiaoyao San had a significant bimodal characteristic when the enzymeeffect curve was decreased. The td, t1 / 2 (ED), AUC and MRT were 17.79 h, 3.73 h, 657.07 UL-1.h-1, (Day), 24.30 h, 3.50 h, 810.19 UL-1.h-1, 19.19 h (night), day-night td and AUC were statistically significant. Conclusion: Xiaoyaosan pharmacokinetics of rats with liver injury there is a diurnal difference, at the end of the rest, the beginning of the activity (8:00) to Xiaoyaosan more reasonable.