Modeling of Absorption

Absorption takes place when a compound enters an organism, which occurs as soon as the molecules enter the first cellular bilayer(s) in the tissue(s) to which is it exposed. At that point, the compound is no longer part of the environment (which includes the alimentary canal for oral exposure), but has become part of the organism. If absorption is prevented or limited, then toxicological effects are also prevented or limited. Thus, modeling absorption is the first step in simulating/predicting potential toxicological effects. Simulation software used to model absorption of compounds of various types has advanced considerably over the past 15 years. There can be strong interactions between absorption and pharmacokinetics (PK), requiring state-of-the-art simulation computer programs that combine absorption with either compartmental pharmacokinetics (PK) or physiologically based pharmacokinetics (PBPK). Pharmacodynamic (PD) models for therapeutic and adverse effects are also often linked to the absorption and PK simulations, providing PK/PD or PBPK/PD capabilities in a single package. These programs simulate the interactions among a variety of factors including the physicochemical properties of the molecule of interest, the physiologies of the organisms, and in some cases, environmental factors, to produce estimates of the time course of absorption and disposition of both toxic and nontoxic substances, as well as their pharmacodynamic effects.