摘要
食物摄入会导致人体胃肠道的生理状况发生各种变化,如胃肠道pH、离子强度、缓冲容量、胃排空时间、内脏血流及代谢酶等。这些变化可通过改变药物的释放、吸收、分布、代谢和/或排泄来影响药物的药动学特征。因此,了解食物是如何改变人胃肠道的管腔状况以及如何对药物的生物利用度产生影响对于药物的临床研究及食物影响的预测具有重要的作用。本文在对临床试验数据库数据总结和文献回顾的基础上,对国家药品监督管理局(NMPA)、美国FDA、欧洲EMA相关临床试验指导原则进行了对比总结,并以抗肿瘤药物为例统计分析了近10年在中国登记注册的对食物影响展开研究的临床试验,综述了新药研发中食物影响的相关因素、指导原则及研究现状,希望能为中国药物上市的发展提供一定的基础研究数据。
The intake of food could lead to various changes in the physiology of human gastrointestinal tract,such as the pH of the gastrointestinal,ionic strength,buffer capacity,the time of gastric emptying,visceral blood flow,and the metabolizing enzymes.These physiological changes would have effects on the release,absorption,distribution,metabolism,and/or excretion of a drug,leading to changes in its pharmacokinetics.Therefore,it is of great importance for clinical research and prediction of the food effect on novel drugs to understand the manner of change in the luminal condition of human gastrointestinal caused by food intake,as well as the manner of the effect on bioavailability.In this paper,we summarized the clinical trials about the food effect on drugs in clinical trial databases and literature first.Then,the guidelines relevant to clinical trials on food effect issued by the National Medical Products Administration(NMPA)of China,the United States FDA,and EMA were compared and summarized.Finally,taking the antitumor novel drugs as an example,we summarized and analyzed the clinical trials about food effect registered in China in the past 10 years,focusing on the main factors related to the food effect in the development of novel drugs,the official guidelines,as well as the current status of research in China,aiming to provide basic research data about the food effect for the development of novel drugs in China.
作者
张艳宝
高慧桃
崔馨戈
任建伟
王维聪
郑昕
ZHANG Yan-bao;GAO Hui-tao;CUI Xin-ge;REN Jian-wei;WANG Wei-cong;ZHENG Xin(Clinical Pharmacology Research Center,Peking Union Medical College Hospital,State Key Laboratory of Complex Severe and Rare Diseases,NMPA Key Laboratory for Clinical Research and Evaluation of Drug,Beijing Key Laboratory of Clinical PK&PD Investigation for Innovative Drugs,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Clinical Trial Center,Beijing Tiantan Hospital Affiliated to Capital Medical University,Bejing 100070,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2023年第18期1843-1849,共7页
Chinese Journal of New Drugs
基金
中央高水平医院临床科研业务费资助(2022-PUMCH-A-247)
首都卫生发展科研专项(2022-2Z-4016)。
关键词
食物影响
胃肠道管腔环境
生物利用度
抗肿瘤药
指导原则
food effect
gastrointestinal cavity environment
bioavailability
antitumor drug
guidance
