Non-specific binding of compounds in metabolism assays: a comparison of microsomal and hepatocyte binding in different species and an assessment of the accuracy of prediction models.

Non-specific binding in metabolism systems leads to an underestimation of the true intrinsic metabolic clearance of compounds being studied. Therefore binding needs to be accounted for when extrapolating data to predict the metabolic clearance of a compound. While techniques exist for experimentally determining the fraction of a compound unbound in metabolism systems, early in drug discovery programmes computational approaches are often used to estimate the binding in the system.