NONMEM7.5.1■中常用参数估计方法比较:以布洛芬注射液在中国健康成年人群的分析为例  

Comparison of common parameter estimation methods in NONMEM 7.5.1■:A case study of ibuprofen injection in Chinese healthy adult population

作　　者：罗铭杰 刘润菡 周杰[1] 王振磊 LUO Mingjie;LIU Runhan;ZHOU Jie;WANG Zhenlei(College of Mathematics,Sichuan University,Chengdu 610064,Sichuan,China;Department of Clinical Medicine(Department of Pharmacy),West China Hospital,Sichuan University,Chengdu 610041,Sichuan,China;Clinical Trial Center of West China Hospital,Sichuan University,Chengdu 610041,Sichuan,China)

机构地区：[1]四川大学数学学院,四川成都610064 [2]四川大学华西医院临床药学部(药剂科),四川成都610041 [3]四川大学华西医院临床试验中心,四川成都610041

出　　处：《中国临床药理学与治疗学》2023年第3期290-298,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金青年课题(No.81903722);四川省科技厅项目(2020YFS0034)

摘　　要：NONMEM®是一款被广泛用于群体药代动力学与药效动力学领域的软件,主要用于做相关的数据分析。它理论上主要通过建立参数化模型,结合已得到的数据,利用不同的参数估计方法,对模型中的参数进行估计后,再根据模型对数据进行预测等分析。本文简要介绍了NON-MEM®中参数化模型的表示形式,并且从统计理论出发,总结了在随机化效应参数与没有交互的条件下,分析了常用的三种参数估计方法。对于非线性混合效应模型,在加和型个体内模型与比例型个体内模型特例下,给出了三种参数估计方法之间的关系。除此之外,通过对四家制药公司关于布洛芬药物浓度随时间变化的数据进行数值实验,从计算时间以及模型预测残差两方面,进一步验证了理论的合理性。NONMEM®is a software widely used in the field of population pharmacokinetics and pharmacodynamics,mainly for related data analysis.In theory,it mainly establishes a parameterized model,combines the obtained data,and uses different parameter estimation methods to estimate the parameters in the model,and then analyzes the data according to the model.This paper briefly introduces the representation of parameterized models in NONMEM■,and from statistical theory,summarizes three commonly used parameter estimation methods under the condition that the randomization effect parametersηandϵdo not interact.For nonlinear mixed effects models,the relationships among three parameter estimation methods are given under special cases of addictive intraindividual models and proportional intra-individual models.In addition,through numerical experiments on data of four pharmaceutical companies on the change of ibuprofen drug concentration with time,the rationality of theory is further verified in terms of calculation time and model prediction residuals.

关 键 词：NONMEM■ 非线性混合效应模型 参数估计 

分 类 号：G623.5[文化科学—教育学] R969[医药卫生—药理学]