A PHYSIOLOGICALLY-BASED MODEL FOR GASTROINTESTINAL ABSORPTION AND EXCRETION OF CHEMICALS CARRIED BY LIPIDS

Pharmacokinetic models which incorporate independently measured anatom ical characteristics and physiological flows have been widely used to predict the pharmacokinetic behavior of drugs, anesthetics, and other chemicals. Models appearing in the literature have included as many as 18,(1) or as few as 5 tissue compartments.(2) With the exception of t he multiple-compartment delay trains used by Bischoff(3) to model the delays inherent to the appearance of drug metabolites in bile and segm ents of the intestinal lumen, very little effort has been made to inco rporate the available information on gastrointestinal anatomy and phys iology into more accurate gastrointestinal absorption/enterohepatic re circulation submodels. Since several authors have shown that the lymph atic system is the most significant route of absorption for highly lip ophilic chemicals, we have constructed a model of gastrointestinal abs orption that emphasizes chylomicron production and transport as the mo st significant route of absorption for nonvolatile, lipophilic chemica ls. The absorption and distribution of hexachlorobenzene after intrave nous vs. oral dosing are used to demonstrate features of this model.