异烟肼在肺结核病患者中的群体药物动力学研究  

Population Pharmacokinetics of Isoniazid in Chinese Tuberculosis Patients

作　　者：陈丽芳[1] 陈镕 黄淑萍[1] 梅早仙[1] 张洁[1] 白志宇[1] 卢炜[2] CHEN Li-fang;CHEN Rong;HUANG Shu-ping;MEI Zao-xian;ZHANG Jie;BAI Zhi-yu;LU Wei(Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine Tianjin Haihe Hospital, Tianjin 300350, China;School of Pharmaceutical Sciences, Peking University, Beifing 100191, China)

机构地区：[1]天津市海河医院,国家中医药管理局中医药防治传染病重点研究室,天津300350 [2]北京大学药学院,北京100191

出　　处：《中国药学杂志》2017年第24期2185-2191,共7页Chinese Pharmaceutical Journal

基　　金：天津市卫生局基金项目资助(2013KZ044)

摘　　要：目的建立异烟肼在中国肺结核患者中的群体药物动力学模型。方法收集201例异烟肼化疗的肺结核患者不同时间血样321份以及相应的生理、病理实验室数据,运用非线性混合效应模型建立异烟肼在该患者群的群体药物动力学模型。考察身高、体重、年龄、性别、剂量、合并用药、血生化等因素对异烟肼在该人群中的药物动力学行为的影响,建立异烟肼的群体药物动力学模型。模型验证采用经预测校正的可视化预测检验。结果带有一级吸收、线性消除的二室模型对异烟肼的血药浓度拟合最好。通过MIXTURE模型区分的"亚群A"和"亚群B"的异烟肼药物动力学行为存在显著差异,群体清除率典型值分别为82.7和19.3 L·h^(-1)。结论模型验证结果表明,所建模型可以对异烟肼在中国肺结核患者中的药物动力学行为进行较好的描述,并可用于个体化给药的指导。OBJECTIVE To characterize the population pharmacokinetics of isoniazid in Chinese tuberculosis patients. METH- ODS A total of 321 serum samples were obtained from 201 patients receiving oral doses of isoniazid. The effects of 16 covariates in- cluding demographics and blood tests to isoniazid＇s pharmacokinetics were evaluated. Data analysis was performed using non-linear mixed effects modeling （NONMEM）. Prediction-corrected visual prediction check was performed for model evaluation. RESULTS A two-compartment model with first-order absorption and linear elimination can well fit the isoniazid concentration-time data. A ＂MIX- TURE＂ model was used to separate the subpopulation of ＇ subgroup A＇ and ＇ subgroup B＇. Typical clearance of the two subpopulations were 82. 7 and 19. 3 L · h^-1 , respectively. CONCLUSION Model validation shows the final model is reliable, which could be used for individualized treatment.

关 键 词：异烟肼 群体药物动力学 非线性混合效应模型 肺结核 

分 类 号：R969.1[医药卫生—药理学]