体内外方法快速筛选系列候选化合物的药动学性质  

Rapid pharmacokinetics screening of drug candidates in vitro and in vivo

作　　者：董晓娜[1,2] 朱晓霞[1] 孟志云[1] 刘江林[1,2] 曹颖林[2] 窦桂芳[1] 

机构地区：[1]军事医学科学院野战输血研究所,北京100850 [2]沈阳药科大学,辽宁沈阳110016

出　　处：《药学学报》2009年第11期1309-1312,共4页Acta Pharmaceutica Sinica

基　　金：国际科技合作重点项目计划资助项目(2005DFA30080)

摘　　要：天然药物分离提取技术和组合化学等技术的发展，大大加快了候选药物的发现速度，每年都有成千上万的新化合物需要进行筛选。药代动力学是药物筛选中至关重要的一个环节，统计数据表明，在药物开发阶段，大约有39％的候选化合物由于药代动力学方面的原因被淘汰，随着体内外筛选技术的发展已经下降到10％。因此，在新药开发的早期阶段，需要利用各种体内和体外模型对候选化合物药动学特点进行初筛，以便在研究开发的早期确定该候选化合物是否有继续开发的价值，The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.

关 键 词：快速筛选 代谢稳定性 生物利用度 LC-MS/MS 

分 类 号：R969[医药卫生—药理学]