肠溶制剂餐后生物等效性试验中的考虑  

Considerations on postprandial bioequivalence study of enteric-coated preparations

作　　者：马婧怡 贺锐锐 王骏 MA Jing-yi;HE Rui-rui;WANG Jun(Centre for Drug Evaluation,National Medical Products Administration,Beijing 100022,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国临床药理学杂志》2022年第18期2244-2248,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：肠溶制剂的释药行为受制剂及体内环境等因素影响较大,一直以来都是仿制药研制过程中较为困难的一类制剂。尤其在餐后生物等效性试验中,由于进食后生理条件发生改变,肠溶制剂释药行为及药代动力学特征变异增大,生物等效性试验常面临不等效的风险。本文将对肠溶制剂餐后生物等效性试验中药代动力学参数变异增大、个别受试者检测不到活性成分浓度或检测活性成分浓度过低、血药浓度达峰时间较其他受试者显著延后等问题产生的原因进行分析,并探讨解决方案。同时,对离群数据的处理进行了探讨。本文可为肠溶制剂生物等效性试验中遇到的挑战提供参考。The release behavior of enteric-coated preparations is greatly affected by factors such as preparation products and in vivo environment.Enteric-coated preparations have always been a difficult class of preparations in the development of generic drugs.Especially in postprandial bioequivalence studies,the variations of release behavior and pharmacokinetic characteristics of enteric-coated preparations increase due to the changes in physiological conditions after meal,thus bioequivalence studies often face the risk of non-equivalence.In this article,the discussions on postprandial bioequivalence study of enteric-coated preparations will be focused on the increased variability of pharmacokinetic parameters,the undetectable or trace concentrations of active ingredients in individual subjects,and the significant delay in time to maximum drug concentration compared with other subjects.The reasons of these phenomena will be investigated,and solutions will be explored.At the same time,the processing of outlier data in postprandial bioequivalence studies will also be discussed.This article can provide a reference for the challenges encountered in bioequivalence studies of enteric-coated formulations.

关 键 词：肠溶制剂 餐后 生物等效性试验 变异 离群数据 

分 类 号：R95[医药卫生—药学]