Zebrafish Cytochrome P450 Assays for Assessing Drug Metabolism and Drug Safety

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DESCRIPTION (provided by applicant): Cytochrome P450 (CYP) enzymes catalyze the majority of known drug metabolism and the bulk of these reactions occur in the liver. As a consequence, many clinically relevant drug-drug interactions are associated with inhibition and/or induction of a specific CYP enzyme. Modifications of CYP activities can have profound effects on therapeutic efficacy and can lead to life-threatening toxicity. In order to provide an early warning system for potential serious side effects, detection of specific CYPs responsible for drug metabolism and drug-drug interactions is a goal of all pre-clinical studies. An ideal CYP assay should be rapid, robust, reliable, reproducible, and amenable to automation in multiwell plate formats. This research will develop a microplate format high throughput whole zebrafish CYP functional assay for assessing drug metabolism and drug safety. Based on genetic and physiological similarity to humans, zebrafish show promise as an efficient, predictive animal model for assessing drug metabolism and drug safety. The zebrafish assay will facilitate detection of specific cytochromes responsible for drug metabolism and drug-drug interactions, and provide an early warning system for potential serious side effects,