A dispersion model of hepatic elimination: 3. Application to metabolite formation and elimination kinetics

A dispersion model of hepatic elimination is presented to describe metabolite formation and elimination kinetics within the liver, consistent with the known physiology and biochemistry of this organ. The model is based on the spread in residence times of blood flowing through the liver. This dispersion model is shown to be more consistent with transient and steady-state data obtained after the single passage of phenacetin and acetaminophen through the liver (both normal and retrograde perfusions) than other models of hepatic elimination. The dispersion model is suitable for the evaluation of enzyme heterogeneity using experimentally obtained metabolite data.