药物代谢清除率体外预测模型研究进展与问题分析  

Advances and related issues in the use of in vitro methods to predict metabolic clearance rate of new drugs

作　　者：张倩[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》2007年第10期1023-1028,共6页Acta Pharmaceutica Sinica

基　　金：国家高技术研究发展计划(863计划)资助项目(2003AA2Z347A;2005AA2Z3C70).

摘　　要：本文介绍了药物代谢清除率临床前预测的相关理论和数学模型,从而将所得的体外代谢清除率数据用于肝清除率的推算,并根据国内外学者对该预测方法准确度评估及体内体外相关性考察,指出该研究领域中出现的难点和可能的改进方案;以期使体内代谢行为的预测更加准确,并对尽早确定创新药物在人体内药物代谢动力学行为是否适合进行进一步研究开发具有重要的指导意义,并为今后创新药物的研发提供新的思路。The reasonable prediction of metabolic clearance rate from the humanized in vitro system is valuable in drug discovery, which is commonly used in the identification and optimization of compounds that mostly like to process appropriate pharmacokinetic characteristics in humans. A detailecl development of the general theory and, models underlying the prediction of in vivo hepatic drug metabolism from in vitro data were presented. Furthermore, the accuracy when extrapolating from in vitro data considering the in vitro-in vivo correlation, method-logical issues and potential solutions were discussed as well. This review can give us a better insight into exploring methods whereby human clearance can be accurately predicted from in vitro data in the process of new drug development.

关 键 词：代谢清除率 药物代谢动力学 体内-体外相关性 

分 类 号：R969[医药卫生—药理学]