The right compound in the right assay at the right time: an integrated discovery DMPK strategy.
The high rate of attrition during drug development and its associated high research and development (R&D) cost have put pressure on pharmaceutical companies to ensure that candidate drugs going to clinical testing have the appropriate quality such that the biological hypothesis could be evaluated. To help achieve this ambition, drug metabolism and pharmacokinetic (DMPK) science and increasing investment have been deployed earlier in the R&D process. To gain maximum return on investment, it is essential that DMPK concepts are both appropriately integrated into the compound design process and that compound selection is focused on accurate prediction of likely outcomes in patients. This article describes key principles that underpin the contribution of DMPK science for small-molecule research based on 15 years of discovery support in a major pharmaceutical company. It does not aim to describe the breadth and depth of DMPK science, but more the practical application for decision making in real-world situations.
AstraZeneca, Alderley Park, UK. peter.ballard@astrazeneca.com
Peter
P
Ballard
Patrick
P
Brassil
Khanh H
KH
Bui
Hugues
H
Dolgos
Carl
C
Petersson
Anders
A
Tunek
Peter J H
PJ
Webborn
D000818:Animals; D003659:Decision Making, Organizational; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004345:Drug Industry / Q000379:methods*; D004347:Drug Interactions; D015507:Drugs, Investigational / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008658:Inactivation, Metabolic; D008657:Metabolic Clearance Rate
D015507:Drugs, Investigational