Snapshot PK: a rapid rodent in vivo preclinical screening approach

被引:53
作者
Liu, Bo [1 ]
Chang, Jonathan [1 ]
Gordon, William P. [1 ]
Isbell, John [1 ]
Zhou, Yingyao [1 ]
Tuntland, Tove [1 ]
机构
[1] Genom Inst Novartis Res Fdn, Dept Pharmacol, San Diego, CA USA
关键词
D O I
10.1016/j.drudis.2007.10.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Described in this article are strategies implemented to increase the throughput of in vivo rodent pharmacokinetic (PK) studies using the snapshot PK study design and automated methods for compound submission, sample processing, data analysis and reporting. Applying snapshot PK studies to categorize the oral exposure of >1300 discovery compounds as low, moderate or high resulted in an attrition rate of 86%. The follow up full PK studies on the remaining compounds found that 98% of the compounds were predicted in the correct (69%) or adjacent (29%) oral exposure category by the snapshot PK studies. These results demonstrate that the snapshot PK screen in rodents can serve as an effective and efficient in vivo tool in the compound selection process in drug discovery.
引用
收藏
页码:360 / 367
页数:8
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