基于大鼠脑缺血再灌注损伤模型建立芍药内酯苷的PK-PD模型

目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。

Pharmacokinetic-Pharmacodynamic Link Model of Albiflorin Based on Cerebral Ischemia-Reperfusion Injury Model Rats

Objective] The aim was to establish the pharmacokinetic-pharmacodynamic(PK-PD) model of albiflorin in Xinshao formula. Method] Firstly, in order to get the drug-time curve of albiflorin in Xinshao formula in plasma collected from different time points of a disease model animal, whose concentration were determined by the method of UPLC-MS.At the same time, the content of SOD and LDH in the plas-ma samples of different time points were determined by the kit for time-effect curve.Then the pharmacokinetic software was used to fit the pharmacokinetic parameters of albiflorin with the compartmental model and to get PK parameters.After that, the pharmacokinetic parameters were fixed, and the time effect relationship were fitted to get the relevant PD parameters.According to the PD parameters, the PK-PD model of albiflorin had been established .Result] When SOD was used as the index of efficacy , the PK-PD model of albiflorin was obtained as E=21.04+(7.16 ×Ce)/(Ce+372.4);When LDH was used as the index of efficacy , the PK-PD model of albiflorin was obtained as E=216.83-(37.31 × Ce)/(Ce+0.04).Conclusion] The PK-PD model of albiflorin in the formula showed that the concentration of SOD and LDH was correlated with the concentration of albiflorin .Albiflorin could protect cerebral ischemia reperfusion injury by increasing SOD and decreasing LDH .