A modern in vivo pharmacokinetic paradigm: combining snapshot, rapid and full PK approaches to optimize and expedite early drug discovery

• Published in: Drug discovery today Vol. 18; no. 1-2; pp. 71 - 78
• Main Authors: Li, Chun, Liu, Bo, Chang, Jonathan, Groessl, Todd, Zimmerman, Matthew, He, You-Qun, Isbell, John, Tuntland, Tove
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2013
• Subjects: Animals; Drug Design; Drug Discovery - methods; Drug Evaluation, Preclinical - methods; Humans; Models, Biological; Pharmaceutical Preparations - metabolism; Pharmacokinetics
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2012.09.004

► Three tiered in vivo rodent PK approaches (snapshot, rapid and full PK studies) at GNF are described. ► Applications and utilities of each in vivo PK approach are discussed. ► PK approaches expedite compound profiling and guide selection into efficacy models. ► Integration of tiered in vitro and in vivo PK approaches into drug discovery paradigm is highlighted. Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches implemented at the Genomics Institute of the Novartis Research Foundation (GNF), which includes snapshot PK, rapid PK and full PK studies. These in vivo PK approaches are well integrated within discovery research, allow tremendous flexibility and are highly efficient in supporting the diverse needs and increasing demand for in vivo profiling. The tiered in vivo PK studies expedite compound profiling and help guide the selection of more desirable compounds into efficacy models and for progression into development.