药物代谢清除率体外预测模型研究进展与问题分析.pdfVIP

药学学报 A cta Pharm aceu tica Sin ica 2007, 42 ( 10) : 1023 - 1028 10·23 · 药物代谢清除率体外预测模型研究进展与问题分析 张 　倩 , 王广基 (中国药科大学 药物代谢动力学重点实验室 , 江苏 南京 2 10009) 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 。 关键词 : 代谢清除率 ; 药物代谢动力学 ; 体内体外相关性 中图分类号 : R969　　　文献标识码 : A 　　　文章编号 : 0513 - 4870 (2007) 10 - 1023 - 06 Advances and rela ted issues in the use of in vitro m ethods to pred ict m etabolic clearance ra te of new drugs ZHAN G Q ian , WAN G Guangj i ( Key L abora tory of D rug M etabolism and P ha rm acok inetics, Ch ina P ha rm aceu tica l Un ivers ity, N anj ing 2 10009, Ch ina) A b stract: The rea sonab le p rediction of m etabo lic clearance rate from the hum an ized in vitro system is valuab le in drug discovery, wh ich is common ly u sed in the iden tification and op tim ization of compound s that mo stly like to p roce ss app rop riate p harm acok inetic characteristic s in hum an s. A detailed developm en t of the general theory and models underlying the p red iction of in vivo hep atic drug m etabo lism from in vitro data were p re sen ted. Fu rthermore, the accu racy when extrapo lating from in vitro data con sidering the in vitroin vivo correlation , m ethodlogical issue s and poten tial so lu tion s were discu ssed a s well. Th is review can give u s a better in sigh t in to exp loring m ethod s whereby hum an clearance can be accu rately p redicted from in vitro data in the p roce ss of new