The intrinsic hepatic clearance reflects the inherent ability of hepatocytes or other subcellular systems (e.g., microsomes, S9 fractions) to eliminate unbound drug and – once corrected for non-specific binding in the incubation – is governed solely by the activity of metabolizing enzymes.
The use of in vitro metabolic clearance data from hepatocytes is a key approach to predict pharmacokinetics by in vitro-in vivo extrapolation (IVIVE) both in humans and animals.
The intrinsic clearance of a drug candidate can be performed in the absence or presence of serum (in order to avoid unspecific adsorption). The unbound intrinsic clearance, considering the hepatocyte and plasma/serum protein binding in the assay medium, is calculated and can be used to predict hepatic blood clearance in humans by applying the well-stirred liver model.
Our assay is generally conducted with unlabeled test compounds using cryopreserved human, minipig, dog, monkey, rabbit, rat, or mouse hepatocytes in suspensions (other species or test systems from special patient populations upon request).