Advances in predicting CYP-mediated drug interactions in the drug discovery setting.

Advances in high-throughput screening methodologies, biological reagents and in silico techniques relating to cytochrome p450 (CYP)-mediated drug-drug interactions have led to reduced clinical attrition rates and to the development of safer therapeutics. Greater understanding of the impact of genetic variability and CYP induction on drug interactions, particularly for low therapeutic index drugs, has facilitated improved clinical study design. This review outlines recent developments using in vitro and in silico technologies to study CYP-mediated drug interactions and describes how those tools have been combined to drive improved candidate selection and in vivo predictions early in the drug discovery process.