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Subcellular fractions are widely used in drug discovery and preclinical drug development to evaluate the in vitro metabolism of drug candidates. Metabolic stability, in vitro intrinsic clearance, reaction phenotyping and inhibition of CYP and UGT enzymes can all be evaluated with subcellular fractions. Subcellular fractions from animals treated with prototypical enzyme inducers can be used to support enzyme induction studies in mice, rats, dogs and monkeys.
Liver subcellular fractions from humans and toxicologically relevant species (mice, rats, rabbits, dogs and monkeys) are widely used to evaluate species differences and similarities in metabolite formation (metabolite profiling). Subcellular fractions from liver and small intestine are used to examine the potential for first-pass (pre-systemic) metabolism of orally administered drugs. Subcellular fractions from small intestine, kidney and lung are often used to evaluate the potential for extrahepatic metabolism of a drug candidate.