磷酸芬戈莫德在健康受试者中的群体药代动力学研究  

Population pharmacokinetics of fingolimod phosphate in healthy subjects

作　　者：陈超阳[1] 董秀 魏然 武元[2] 张捷[2] 常旭婷 吴晔[2] 周颖[1,4] 崔一民[1,3,4] CHEN Chao-yang;DONG Xiu;WEI Ran;WU Yuan;ZHANG Jie;CHANG Xu-ting;WU Ye;ZHOU Ying;CUI Yi-min(Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China;Department of Pharmacy Administration and Clinical Pharmacy,School of Pharmaceutical Science,Peking University,Beijing 100191,China)

机构地区：[1]北京大学第一医院药学部,北京100034 [2]北京大学第一医院儿科,北京100034 [3]北京大学第一医院临床药理研究所,北京100034 [4]北京大学药学院药事管理与临床药学系,北京100191

出　　处：《中国临床药理学杂志》2023年第15期2237-2240,共4页The Chinese Journal of Clinical Pharmacology

基　　金：科技重大专项重大新药创制“十三五”课题基金资助项目(2017ZX09304029-006-001)。

摘　　要：目的建立磷酸芬戈莫德在健康人中的群体药代动力学(PPK)模型,为个体化用药提供参考。方法用基于模型的荟萃分析方法,检索PubMed、EmBase、Cochrane Library、中国知网及万方数据库中磷酸芬戈莫德的药代动力学(PK)研究,采集研究的基础信息、给药信息、采血信息、检验检查信息、合并用药信息以及磷酸芬戈莫德血药浓度-时间数据。用非线性混合效应模型法建立磷酸芬戈莫德的PPK模型,考察种族、性别、年龄、体质量、体质量指数(BMI)、进食情况以及合并用药对于磷酸芬戈莫德PK参数的影响。结果共纳入11项磷酸芬戈莫德相关研究,包含23个研究组(对应354例受试者)的167条血药浓度-时间数据。具有一级吸收的一室模型可以充分描述磷酸芬戈莫德的PK特征。清除率和表观分布容积的群体典型值分别为6.41 L·h^(-1)和4.70 L。研究考察的协变量对磷酸芬戈莫德PK参数无显著影响。结论一室模型可以充分描述磷酸芬戈莫德的PK特征,种族、性别、年龄、体质量、BMI、进食情况等因素不是磷酸芬戈莫德PK的显著协变量,无需依据上述因素调整芬戈莫德的用药方案。Objective To establish a population pharmacokinetic(PPK)model of fingolimod phosphate in healthy subjects in order to provide reference for individualized fingolimod use.Methods A model-based meta-analysis method was used.Fingolimod pharmacokinetic(PK)studies were searched from PubMed,EmBase,Cochrane Library,CNKI and WANFANG databases,and the basic information,drug administration information,blood collection information,test information,drug combination information and blood concentration-time data of fingolimod phosphate were extracted.The PPK model was established by nonlinear mixed-effect approach.The effects of race,sex,age,body weight,body mass index(BMI),diet and drug combination on PK parameters of fingolimod phosphate were investigated.Results A total of 11 fingomode phosphate studies were included,including 167 blood concentration-time data from 23 study groups(corresponding to 354 subjects).A one-compartment model with first-order absorption could adequately describe the PK characteristics.The population typical values of clearance and apparent volume of distribution were 6.41 L·h^(-1) and 4.70 L,respectively.The covariates examined in this study had no significant effect on the PK parameters of fingomode phosphate.Conclusion A one-compartment model can fully describe the PK characteristics of fingolimod phosphate.Race,sex,age,body weight,BMI,food intake and other factors are not significant covariates,and there is no need to adjust fingomode dosing regimen based on the above factors.

关 键 词：芬戈莫德 磷酸芬戈莫德 群体药代动力学 基于模型的荟萃分析 

分 类 号：R971[医药卫生—药品]