摘要
目的:建立美罗培南在老年人体中生理药动学模型,为老年人临床用药提供指导。方法:查阅相关文献,获得美罗培南的药物理化性质及吸收、分配、代谢和排泄等特异参数,及健康成人和老年人美罗培南静脉注射PK研究数据。利用PK-Sim®软件建立成人生理药动学(physiologically based pharmacokinetic,PBPK)模型并外推至老年人群体。采用平均折叠错误(mean fold error,MFE)法比较C_(max)、T_(max)、AUC_(0-∞)预测与实测值之间差异,以评估PBPK模型的准确性,并模拟肾功能不全的老年人群PK研究进行剂量推荐。结果:建立的美罗培南成人PBPK模型,其AUC和C_(max)的MFE值皆在0.5和2以内。所有老年人PBPK模型符合0.5<MFE值<2的标准要求。相对于健康成人,老年人需要更小剂量的美罗培南以达到相同的血浆暴露水平,肾功能不全的老年人群体拥有更大的PK变异。结论:本研究建立的美罗培南成人PBPK模型可以外推至老年人群体,为老年人临床个性化用药提供参考。
OBJECTIVE To establish a model of meropenem in elders to provide guidance for clinical use of meropenem.METHODS The relevant literatures were consulted to obtain the physicochemical constants of meropenem and such specific parameters as absorption,distribution,metabolism and excretion,as well as PK research data of intravenous meropenem in healthy adults and elders.A physiologically based pharmacokinetic(PBPK)model was established using PK-Sim®software and subsequently extrapolated to an elderly population.Mean fold error(MFE)method was employed for comparing the differences between predicted and measured values of pharmacokinetic parameters C_(max),T_(max),AUC_(0-∞)to evaluate the accuracy of PBPK model.And PK study was simulated for dose recommendation in elders with renal dysfunction.RESULTS The adult PBPK model of meropenem was successfully established and MFE values of AUC and C_(max)were both within 0.5 and 2.All PBPK models of elders fulfilled the standard requirement of 0.5<MFE value<2 and the PBPK model of elders was successfully established.Elders required a lower dose of meropenem for achieving the same plasma exposure levels as healthy adults.Furthermore,elders with renal dysfunction had a larger PK variation.CONCLUSION The adult PBPK model of meropenem may be extrapolated to elders.This study provides a reference for realizing clinical personalized medication for elders.
作者
杨玉洁
徐敏
郗恒
徐超然
崔芬芳
张晞倩
郑雅娴
何琴
YANG Yu-jie;XU Min;XI Heng;XU Chao-ran;CUI Fen-fang;ZHANG Xi-qian;ZHENG Ya-xian;HE Qin(Department of Pharmacy,Third Municipal People's Hospital,Sichuan Chengdu 610000,China)
出处
《中国医院药学杂志》
CAS
北大核心
2021年第21期2196-2201,共6页
Chinese Journal of Hospital Pharmacy
