ON THE DEGREE OF SOLUTE MIXING IN LIVER MODELS OF DRUG ELIMINATION

One of the fundamental differences between various liver models regard s the underlying assumptions on the intrahepatic mixing process. A mod el-independent method for the evaluation of the departure from the per fectly mixed system is proposed which is based on an application of th e relative entropy concept to hepatic transit time distributions of in travascular markers. This approach provides a measure of the distance between two probability distributions. Available data measured in isol ated 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 equilibriu m model and the physiological irrelevance of the underlying well-stirr ed assumption. In terms of the dispersion model the results are in acc ordance with the model equation obtained for mixed boundary conditions .