生理药动学模型研究利多卡因静脉给药的体内过程

 目的建立血流限速型生理药动学模型,描述与预测在不同病理状态下人体静脉输注利多卡因后药物的体内过程。方法依据药物在体内血流限速的转运特征,在MATLAB/Simulink仿真环境下构建生理药动学模型的模拟平台;引入人体生理参数和利多卡因人体动力学参数,模拟已有报道的利多卡因人体试验给药方案,验证模型有效性,分析主要生理参数对药物体内过程的影响;模拟利多卡因的常规给药方案和不同的病理生理条件,预测各器官组织中药物的经时变化。结果建立了一个包含11个血流限速转运特征的器官(组织)房室的生理模型描述静脉输注利多卡因后药物的体内过程;模型密闭性好,预测值均在试验数据的1倍SD以内,心输出量变化对各器官利多卡因浓度的影响较分配系数、肝清除率的影响显著。结论生理药动学模型预测值与试验结果相符,对利多卡因的临床个体化给药有现实意义。

Study on Physiologically Based Pharmacokinetic Model for Lidocaine Administrated by Intravenous Infusion

OBJECTIVE To develop a physiologically based pharmacokinetic model for lidocaine and to study the effect of different pathological or physiological condition on the kinetics of lidocaine in human.METHODS Using the commercially available programming software MATLAB/SIMULINK, a platform to simulate flow-dependent PBPK models was developed.A perfusionlimited PBPK model representing eleven body organs/tissues for lidocaine administrated by intravenous infusion was developed.Physiological organ flow rates,tissue volumes,and tissue-plasma partition coefficient for lidocaine in human were taken from the literature.RESULTS The simulated arterial lidocaine concentrations were within one standard deviation of all the reported human data.The model was more sensitivity to changes in cardiac output than those in tissue-plasma partition coefficient and hepatic intrinsic clearance.CONCLUSION There is excellent agreement between experimentally observed and model predicted plasma concentrations.The simulation result can be a direction for clinical individual dose regime of lidocaine.