Snapshot PK: a rapid rodent in vivo preclinical screening approach.
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.
Liu
Bo
B
Department of Pharmacology, Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA, USA.
Chang
Jonathan
J
Gordon
William P
WP
Isbell
John
J
Zhou
Yingyao
Y
Tuntland
Tove
T
D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D051379:Mice; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D051381:Rats
D004364:Pharmaceutical Preparations