Biotransformation

QPS provides biotransformation studies to determine how a substance may be altered within the body by the action of enzymes. Among QPS studies to support discovery and development of new drug candidates are these:

• In vitro metabolic stability in hepatic preparations to determine intrinsic clearance

• In vitro comparison of metabolite formation in animal and human hepatic preparations, using non-labeled and radio-labeled test articles

• In vivo metabolite profiling, identification and quantification using samples collected from animals and human mass balance/excretion studies

• In vitro CYP enzyme inhibition in human liver microsomes to determine IC₅₀ and/or K_i

• Time-dependent in vitro CYP enzyme inhibition

• In vitro protein covalent binding assessment using animal and/or human liver microsomes or hepatocytes and in vivo assessment using plasma and liver collected from animals treated with radiolabeled test article

• In vitro CYP enzyme induction using fresh or cryopreserved human hepatocyte cultures

• Ex vivo CYP enzyme induction in livers from animal species such as mice, rats, dogs or monkeys after repeated dose treatment in toxicology studies

• In vitro CYP reaction phenotyping using both chemical inhibitors and cDNA expressed enzymes