体外代谢在新药早期评价中的应用与发展  

Application and development of in vitro metabolism study at early drug discovery stage

作　　者：吴慧[1] 彭英[1] 孙建国[1] 张雪媛[1] 仲云熙[1] 王广基[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,江苏南京210009

出　　处：《药学学报》2013年第7期1071-1079,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30901832);科技基础设施建设计划--创新平台提升项目(BM2012012)

摘　　要：药物代谢研究与新药研发中的诸多环节密不可分,包括候选化合物的设计与先导化合物的筛选等。药物代谢研究一般分为体内代谢研究与体外代谢研究。与体内代谢研究相比,体外代谢研究可直接观察候选化合物与受试靶点的选择性作用,不需要消耗大量的样品和实验动物,操作快速简便,适用于代谢信息不明确的候选化合物进行高通量筛选。目前,体外代谢研究已被广泛应用于新药的早期代谢评价中,主要涉及代谢稳定性、代谢酶亚型鉴定以及代谢性相互作用等。本文就体外代谢研究在上述三方面的具体应用进行归纳总结,为中国创新药物实施"早期评价、早期淘汰"的研究策略提供参考。Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.

关 键 词：体外代谢模型 体外代谢稳定性 体外代谢酶亚型鉴定 体外代谢相互作用 

分 类 号：R969[医药卫生—药理学]