高原缺氧性脑病的非临床药效学评价体系  

Non clinical pharmacodynamic evaluation system of high-altitude hypoxic brain injury

作　　者：刘梦瑶 赵春阳 商廿颍 王庆利 彭英[1] LIU Meng-yao;ZHAO Chun-yang;SHANG Nian-ying;WANG Qing-li;PENG Ying(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Center for Drug Evaluation,National Medical Product Administration,Beijing 100022,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050 [2]国家药品监督管理局药品审评中心,北京100022

出　　处：《药学学报》2023年第6期1515-1520,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81802877);中国医学科学院医学与健康科技创新工程(2021-I2M-1-054,2021-I2M-1-028)。

摘　　要：高原空气稀薄,属于低温、低氧、低压环境,人脑对缺氧最敏感,低压低氧会引发中枢神经系统功能障碍,出现高原缺氧性脑病,临床上包括高原头痛和严重的高原脑水肿。随着越来越多的人工作、生活在高原地区,开发抗高原缺氧性脑病药物具有很大的经济价值和社会意义。非临床药效学评价是药物开发的基础环节,对提高临床转化成功率和降低临床研究风险起到了关键作用。本文总结了高原缺氧性脑病的细胞模型和动物模型,以及用于评价药物药效的检测指标,旨在建立起规范的抗高原缺氧性脑病的非临床药效学评价体系,以期为广大药物研发人员提供参考,提高创新药物的临床转化的成功率。The air at high altitude is thin and belongs to the environment of low temperature,low oxygen and low pressure.The human brain is the most sensitive to hypoxia.Hypoxia will cause dysfunction of the central nervous system,resulting in high-altitude hypoxic brain injury,including mild high altitude headache and more destructive high altitude cerebral edema(HACE).Recently,with more and more people work and live in high altitude areas,the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance.Non clinical pharmacodynamic evaluation is the basic of drug development,which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research.This review summarizes the cell models and animal models,and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury.We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy,and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.

关 键 词：高原缺氧性脑病 非临床药效学评价 新药研发 细胞模型 动物模型 

分 类 号：R966[医药卫生—药理学]