Modeling multifactorial aspects of disease and drug therapy

AbstractA physiological flow model was developed for the elimination of Warfarin and Adriamycin in the rat. The model uses organ mass or volume, blood flow to the organ and tissue to plasma drug distribution ratios to compute unsteady state concentration profiles for each drug. The parameters in the model can be changed to match changes that could occur in liver disease, aging or the influence of coadministered drugs used for other therapeutic purposes. Elimination rates may be reduced by liver damage, reduced liver function, altered circulation rates or altered tissue binding resulting from disease or aging. Coadministered drugs could inhibit the elimination of the primary drug via competition for a common site, or could also diminish elimination by producing liver damage. Drug elimination could be enhanced by enzyme induction. These effects have been studied experimentally and simulated using computer programs