Predicting drug-drug interactions in drug discovery: where are we now and where are we going?
Pressure on drug discovery research teams to identify successful drug candidates earlier on in the drug discovery process has led to the development of a variety of ADME in vitro assays, intended to guide chemists and biologists in their decision-making process. The role of these early assays is to indicate liabilities in scaffolds relating to the absorption, distribution, metabolism and cytochrome P450 (CYP) inhibition potential of new chemical entities. Current efforts in drug-drug interaction (DDI) screening can be divided into four basic categories: bioanalytical method development, strategies relating to enzyme kinetics, recognition of CYP allelic variants and generation of computational models to predict CYP interactions. Collectively, DDI screening represents an important means not only for assessing and ranking potential drug candidates, but also for aiding in the development of mechanisms for predicting and retrospectively explaining in vivo drug performance.
Hutzler
Matthew
M
Pfizer PGRD Pharmacokinetics, Dynamics and Metabolism, Chesterfield, MO 63017, USA.
Messing
Dean M
DM
Wienkers
Larry C
LC
D000818:Animals; D015195:Drug Design; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005544:Forecasting; D006801:Humans; D007700:Kinetics