Drug Interaction Studies in the Drug Development Process: Studies In Vitro

Determination of the potential effects of new molecules on the activities of drug metabolizing enzymes in vitro can be useful in several areas of drug research. The data can serve as an indicator of whether a new compound could cause pharmacokinetic-based drug-drug interactions. In early research, such assays can be conducted using high-throughput approaches to accommodate the large numbers of compounds synthesized and tested for pharmacological activity (Figure 16.1). To be fit-for-purpose (i.e., development 430of structure-activity relationships, driving compound design), these assays require high capacity and sacrifice some aspects of assay performance to allow for this capacity. Miniaturized methods that use fluorogenic substrates and plate reader platforms ¹ or cocktail methods (in which multiple substrates are mixed and the assays done simultaneously ² are well suited for these needs.