Application Note


Automated 384-Well Cell-Based Cytochrome P450 Inhibition Assays Using Cryopreserved Human Hepatocytes In Suspension

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By Brad Larson and Peter Banks, BioTek Instruments, Inc.
Timothy Moeller, Celsis IVT
Tracy Worzella, Mary Sobol, Dongping Ma, James J. Cali, Promega Corporation

Drug-drug interactions (DDI) are a serious concern to pharmaceutical manufacturers and regulatory agencies. As such, ADME-Tox studies including DDI are tested early in the xenobiotic life cycle. Cytochrome P450 (CYP) enzymes are key drug metabolizers in the body, and therefore play a major role in DDI research and testing. Here we demonstrate an automated assay system, including a luminescent CYP inhibition assay, primary hepatocytes and automated microplate instrumentation, to test lead compound inhibitory effects on CYP isoforms. Validation and pharmacology data, including a comparison to data generated using human liver microsomes, prove that the combination of cells, assay, and instrumentation provide rapid, dependable information on CYP-based drug inhibition in a cell-based format.

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Automated 384-Well Cell-Based Cytochrome P450 Inhibition Assays Using Cryopreserved Human Hepatocytes In Suspension

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