五种群体药动学分析工具计算结果的比较  

Comparison of calculation results of five population pharmacokinetic analysis tools

作　　者：黄志伟 李熠 徐晓勇 张蕾[1] 沈一峰[1] 李华芳[1] HUANG Zhiwei;LI Yi;XU Xiaoyong;ZHANG Lei;SHEN Yifeng;LI Huafang(Clinical Research Center of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200000,China;Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai 200000,China;Department of Pharmacy,Children's Hospital of Fudan University,Shanghai 200000,China)

机构地区：[1]上海交通大学医学院附属精神卫生中心临床研究中心,上海200000 [2]复旦大学附属华山医院抗生素研究所,上海200000 [3]复旦大学附属儿科医院药剂科,上海200000

出　　处：《中国临床药理学与治疗学》2023年第5期525-535,共11页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：上海市精神心理疾病临床医学研究中心(19MC1911100);上海市转化医学协同创新中心(TM202116PT)。

摘　　要：目的:比较群体药动学分析工具Phoenix NLME、Monolix、R语言nlmixr包和CPhaMAS云平台所计算的结果与金标准NONMEM的符合程度。方法:基于一房室模型模拟50个稀疏采样数据集和二房室模型模拟50个密集采样数据集,分别使用上述五种分析工具计算,比较群体典型值、个体变异和个体药动学参数。结果:CPhaMAS和Phoenix NLME计算的群体典型值、个体变异与NONMEM的匹配程度最高,其次为nlmixr,Monolix最低,但Monolix和nlmixr的算法可能更稳健。清除率和分布容积的对应性优于吸收速率常数。除了Monolix计算的吸收速率常数和nlmixr计算的房室间清除率,所有分析工具计算的个体药动学参数相关系数均大于0.99。结论:上述四种群体药动学分析工具计算结果与NONMEM的结果高度相关。AIM:To compare the results calculat-ed by population pharmacokinetic analysis tools Phoenix NLME,Monolix,R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM.METHODS:Fifty sparse sam-pling data sets based on a one-compartment mod-el and fifty dense sampling data sets based on a two-compartment model were simulated,and the above five analysis tools were used to calculate the population typical value,individual variability and individual pharmacokinetic parameters.RESULTS:The population typical value and individual variabil-ity calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM,fol-lowed by nlmixr.Monolix had the lowest matching degree,but Monolix and nlmixr might be more ro-bust.The correspondence between clearance and distribution volume was better than the absorption rate constant.Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr,the correlation coef-ficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99.CONCLUSION:The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.

关 键 词：群体药动学 NONMEM 房室模型 

分 类 号：R969.1[医药卫生—药理学]