放射性同位素标记策略在人体物质平衡试验中的应用进展  

Application progress of radiolabeling strategies in human mass balance studies

作　　者：何伊菲 郑元东 钟大放 刁星星 HE Yi-fei;ZHENG Yuan-dong;ZHONG Da-fang;DIAO Xing-xing(Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 101408,China)

机构地区：[1]中国科学院上海药物研究所,上海201203 [2]中国科学院大学,北京101408

出　　处：《药学学报》2024年第9期2470-2483,共14页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82373938).

摘　　要：物质平衡试验是新药研发过程的一项关键研究,旨在揭示药物在人体内的代谢和排泄路径。目前,人体物质平衡试验主要利用放射性同位素标记技术进行,国内外药品监督管理机构已相继发布了相关的研究草案和指导原则,以鼓励并指导工业界按规范进行研究。放射性标记位点的选择对于获得药物代谢的关键信息极为重要。然而,体内生物转化可能会导致药物分子结构的部分断裂,从而使未标记部分的代谢产物信息丢失。使用不同放射性标记位点的药物分开给药或混合给药,或在一个分子中同时标记多个放射性同位素,可以有效解决这一问题。本文回顾了相关的技术进展,分析了放射性同位素标记策略,并对多个放射性标记位点药物在人体物质平衡试验中的应用进行了讨论。Human mass balance study is a pivotal research in the field of clinical pharmacology,aiming at elucidating the metabolic and excretion pathways of drugs in humans.Currently,human mass balance studies predominantly employ radiolabeling techniques.Recently,both the U.S.Food and Drug Administration(FDA)and the Center for Drug Evaluation(CDE)of the China National Medical Products Administration(NMPA)issued related research drafts and guidelines to encourage and guide the pharmaceutical industry to conduct research in compliance with established standards.The selection of radiolabeling sites is crucial for obtaining critical information on drug metabolism.However,in vivo biotransformation may lead to partial disintegration of the molecular structure,thereby resulting in the loss of metabolic product information of the unlabeled moiety.Administering drugs with different radiolabeling sites separately or in combination,or labeling multiple radioactive isotopes within one molecule,can effectively solve this problem.This article reviews relevant technological progress,analyzes radiolabeling strategies,and discusses the application of drugs with multiple radiolabeling sites in human mass balance studies.

关 键 词：物质平衡 放射性标记 同位素示踪技术 药物代谢 人体放射性试验 

分 类 号：R917[医药卫生—药物分析学]