聚乙二醇修饰药物非临床研究中聚乙二醇相关组织病理学改变及评价关注点  

Polyethylene glycol-related histopathological changes and evaluation considerations in nonclinical studies of polyethylene glycol-modified drugs

作　　者：戎怿 李浩运 李德利 董田甜 孟李凯 宫新江 张慧 闫莉萍 RONG Yi;LI Hao-yun;LI De-li;DONG Tian-tian;MENG Li-kai;GONG Xin-jiang;ZHANG Hui;YAN Li-ping(Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China;TriApex Laboratories Co.,Ltd.,Nanjing 211800,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100022 [2]江苏鼎泰药物研究(集团)股份有限公司,南京211800

出　　处：《中国新药杂志》2024年第19期2033-2037,共5页Chinese Journal of New Drugs

摘　　要：聚乙二醇(polyethylene glycol, PEG)是一种生物相容性高、无空间位阻、具有两亲性的高分子聚合物,经过PEG修饰的药物可降低其在体内的清除率和/或改变药物的分布特征,具有提升药物稳定性、延长作用时间、降低给药频率、减弱抗原性等优势,因此PEG化修饰被广泛应用于多种药物制剂中。在该类药物的非临床组织病理学研究中,经常可观察到与PEG相关的组织空泡化现象,而目前对PEG修饰药物引起空泡化的机制与长期安全性影响认识还不充分。基于此,本文总结了PEG修饰药物常见的组织病理学改变的机制及其主要影响因素,汇总了现有诊断标准和在实践中评估该类组织病理学变化的考虑因素,并提出了PEG修饰药物审评角度的关注点,以期为该类药物的非临床和临床安全性评价提供参考。Polyethylene glycol(PEG)is a biocompatible,non-sterically hindered polymer with amphiphilic properties that is widely used to modify various types of drugs.PEGylation of drugs can decrease their clearance rate and/or alter their distribution characteristics in vivo,thereby promoting stability,prolonging their duration of action in the body,reducing the dosing frequency to maintain the treatment levels,and reducing antigenicity,and so on.Therefore,PEGylation is widely used in various drug formulations.In nonclinical histopathological studies of such drugs,PEG-associated vacuolation is frequently observed.However,the understanding of the mechanism and long-term safety of PEGylated drugs causing vacuolation is currently insufficient.Therefore,this article summarized the mechanism and influencing factors of common histopathological changes associated with PEGylated drugs,compiled existing diagnostic criteria and considerations for evaluating such histopathological changes in practice,and raised concerns from the perspective of PEGylated drugs evaluation.The goal of this article is to provide a reference for nonclinical and clinical safety assessments of PEGylated drugs.

关 键 词：聚乙二醇 聚乙二醇修饰药物 组织病理学改变 空泡化 安全性评价 

分 类 号：R94[医药卫生—药剂学] R965.3[医药卫生—药学]