CELL-BASED MATERIALS AND METHODS FOR DEFINING PHARMACOGENETIC DIFFERENCES IN DRUG METABOLISM

摘要

Cell lines harboring a range of polymorphisms using recombinant cytochrome P450 or other chemical-metabolizing enzymes in a parent cell line that is minimally expressing or devoid of its own cytochrome P450 protein or other chemical- metabolizing enzymes of interest can be placed into an array format to enable high throughput screening of one or more chemicals for CYP450 or other enzyme- dependent metabolism (Fig. 9). Processing of the cells can be automated, done en- masse through use of an array having a substrate upon which a plurality of cell lines with exogenous chemical-metabolizing enzymes are coupled, and both relative and quantitative metabolism rates determined using mass spectrometry over time. Thus, methods are disclosed to measure, for example, the effects of cytochrome P450 polymorphisms on clinical drug metabolism in a high throughput manner for drug development and genetically personalized diagnostics and treatment regimens.