Chapter 8 - Toxicokinetics in Veterinary Toxicology

Abstract

Toxicokinetics refers to the movement and fate, also referred to as the disposition, of toxicants. It includes the processes of absorption, distribution, and elimination (including biotransformation and excretion) of toxicants in an organism. These processes are often described using mathematical models, and such models can be used for predicting plasma and tissue concentrations over time, which is essential for the prediction of adverse effects and for the avoidance of undesirable xenobiotic residues in animal tissues. Relevant parameters that are often derived from models include absorption rate and extent, apparent volume of distribution, clearance and half-life. Certain models can also be used to describe, analyze and, ultimately, understand the specific physiological processes that determine toxicant kinetic parameter values. Two fundamentally different types of toxicokinetic models are recognized: empirical toxicokinetic models, and physiologically based toxicokinetic models. Traditional toxicokinetic models are mathematical descriptions of concentration/time profiles that are constructed without assuming that the compartments and functions used in the models are directly representative of physical structures or physiological processes. The selection of compartments and functions are therefore solely dependent on their ability to simulate experimentally observed concentration/time profiles. Physiologically based toxicokinetic models, on the other hand, are mathematical simulations of kinetic processes in organs and tissues. The mathematical constructs therefore represent actual organs, tissues, and physiological processes.