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Automated 384-Well Cell-Based Cytochrome P450 Inhibition Assays using Cryopreserved Human Hepatocytes in SuspensionDownload
February 02, 2011
Authors: Brad Larson, Peter Banks, BioTek Instruments, Inc., Winooski, Vermont; Timothy Moeller, Celsis In Vitro Technologies, Baltimore, Maryland; Tracy Worzella , Mary Sobol, Dongping Ma, James J. Cali, Promega Corporation, Madison, Wisconsin
The ability to determine the enzymes and processes involved in drug metabolism, as well as the potential modulation of that metabolism, is essential to ensure proper therapeutic outcomes and eliminate potential drug-drug interactions (DDI). Though traditionally performed with microsomes, more recently hepatocytes have been utilized in order to provide more in vivo-like correlations. This desire, coupled with the fact that ADME/Tox assays in general are being run earlier in the drug discovery process, has led to the development of easy-to-use, robust assay chemistries, as well as the instrumentation to perform these assays in a high-throughput format. Here we demonstrate an automated solution to run luminescent CYP450 inhibition assays using primary hepatocytes in a profi ling format for CYP1A2, -2C9, and -3A4. Validation and pharmacology data prove how the combination of cells, assay, and instrumentation provide rapid, dependable information on the inhibition of CYP450- based drug metabolism in a cell-based format.