Application of Cytochrome P450 Drug Interaction Screening in Drug Discovery

Title: Application of Cytochrome P450 Drug Interaction Screening in Drug Discovery

Volume: 13 Issue: 2

Author(s): Robert S. Foti, Larry C. Wienkers and Jan L. Wahlstrom

Affiliation:

Keywords: P450, drug interactions, enzyme inhibition, in silico

Abstract: Advances in drug interaction screening have resulted in reduced compound attrition rates due to unfavorable CYP-mediated drug interactions in clinical trials and improved patient safety. A major driver for the success in predicting drug interactions is a better understanding of the biological, chemical or mechanical factors that can impact the prediction of drug interactions in vitro. The enzyme source, probe substrate, accessory proteins and pharmacogenetics can all have profound effects upon the robustness and relevance of data generated with in vitro drug-drug interaction assays. Furthermore, the use of in silico techniques can potentially afford a priori knowledge of drug interaction potential, thus reducing the time and cost associated with drug interaction screening. This review will focus on recent advances in in vitro, in silico and bioanalytical techniques and demonstrate how these tools are currently used to provide effective CYP drug interaction screening in a discovery setting.

Cite this article as:

Foti S. Robert, Wienkers C. Larry and Wahlstrom L. Jan, Application of Cytochrome P450 Drug Interaction Screening in Drug Discovery, Combinatorial Chemistry & High Throughput Screening 2010; 13 (2) . https://dx.doi.org/10.2174/138620710790596718