On the degree of solute mixing in liver models of drug elimination.

One of the fundamental differences between various liver models regards the underlying assumptions on the intrahepatic mixing process. A model-independent method for the evaluation of the departure from the perfectly mixed system is proposed which is based on an application of the relative entropy concept to hepatic transit time distributions of intravascular markers. This approach provides a measure of the distance between two probability distributions. Available data measured in isolated perfused livers indicate that sinusoidal solute mixing is nearly optimal. The suggestion of maximum mixedness in the liver may explain the discrepancy between the apparent validity of the venous equilibrium model and the physiological irrelevance of the underlying well-stirred assumption. In terms of the dispersion model the results are in accordance with the model equation obtained for mixed boundary conditions.