Figure 1.
In vitro-in vivo extrapolation (IVIVE) scheme where an in vitro incubation of hepatocytes or microsomes allows determination of the half-life of drug elimination and an estimate of the in vitro drug intrinsic clearance (CLint), which is then scaled up to whole organism liver intrinsic clearance. This value is then inserted into an equation representing a model of hepatic elimination, here the purported well-stirred model incorporating whole organism liver blood flow (QH) and fraction unbound in blood (fu,B), with correction for fraction unbound in the incubation mixture (fu,inc), to predict an in vivo liver clearance (CLH).