MASS TRANSFER MODELING OF HEPATIC DRUG ELIMINATION USING LOCAL VOLUME AVERAGING APPROACH

Applying local volume averaging method a mathematical model including liver porosity, tortuosity, permeability, unbound drug fraction, drug-plasma diffusivity, axial/radial dispersion and hepatocellular metabolism parameters was developed for hepatic drug elimination. The model was numerically solved using implicit finite difference method to describe drug concentration gradient with time across the liver. Statistically validated by observations and other models, the model suggested axial dispersion as a significant variable in drug distribution across the liver. Sensitivity analyses revealed that lower liver porosity resulted in faster drug distribution across the liver, and bioavailability was sensitive to the interaction between unbound fraction and intrinsic clearance.