Metabolic stability

Enable accurate prediction of hepatic intrinsic clearance for drug development

Intrinsic hepatic clearance reflects the inherent ability of hepatocytes or other subcellular systems (e.g., microsomes, S9 fractions) to eliminate unbound drugs. Once corrected for non-specific binding in the incubation, it is solely governed by the activity of metabolising enzymes. The intrinsic clearance determination of a drug candidate can be performed in the absence or presence of serum to avoid unspecific adsorption. The unbound intrinsic clearance, considering hepatocyte and plasma/serum protein binding in the assay medium, is calculated and can be used to predict human hepatic blood clearance using the well-stirred liver model. Our assay is typically conducted with unlabeled test compounds using cryopreserved hepatocytes from humans, mini pigs, dogs, monkeys, rabbits, rats and mice. Other species or test systems from special patient populations are available upon request.