Introduction

Toxicokinetics (often abbreviated as 'TK') is the description of both what rate a chemical will enter the body and what occurs to excrete and metabolize the compound once it is in the body. It is an application of pharmacokinetics to determine the relationship between the systemic exposure of a compound and its toxicity. It is used primarily for establishing relationships between exposures in toxicology experiments in animals and the corresponding exposures in humans.

However, it can also be used in environmental risk assessments in order to determine the potential effects of releasing chemicals into the environment. In order to quantify toxic effects toxicokinetics can be combined with toxicodynamics. Such Toxico Kinetic-Toxico Dynamic (TKTD) models are used in ecotoxicology (see ecotoxmodels a website on mathematical models in ecotoxicology).

Toxicokinetics is essentially the study of "how a substance gets into the body and what happens to it in the body." Before this term was used, the study of the kinetics (movement) of chemicals was originally conducted with pharmaceuticals and the term pharmacokinetics became commonly used. Similarly, toxicology studies were initially conducted with drugs. Toxicokinetics deals with what the body does with a drug when given a relatively high dose relative to the therapeutic dose. Read more about differences between pharmacokinetics and toxicokinetics.

Processes

Four processes are involved in toxicokinetics: Absorption: the substance enters the body. Distribution: the substance moves from the site of entry to other areas of the body. Biotransformation: the body changes (transforms) the substance into new chemicals (metabolites). Excretion: the substance or its metabolites leave the body. The science of toxicology has evolved to include environmental and occupational chemicals as well as drugs. Toxicokinetics is thus the appropriate term for the study of the kinetics of all substances at toxic dose/exposure levels.

Frequently the terms toxicokinetics, pharmacokinetics, or disposition have the same meaning. Disposition is often used in place of toxicokinetics to describe the movement of chemicals through the body over the course of time, that is, how the body disposes of a xenobiotic. Assuming that the concentration of a compound in blood or plasma is in equilibrium with concentrations in tissues, then changes in plasma toxicant concentrations should reflect changes in tissue toxicant concentrations.

Pharmacokinetic models

Compartmental pharmacokinetic models consist of a central compartment representing plasma and tissues that rapidly equilibrate with chemical, connected to one or more peripheral compartments that represent tissues that more slowly equilibrate with the chemical. Chemical is administered into the central compartment and distributes between central and peripheral compartments.

Chemical elimination occurs from the central compartment, which is assumed to contain rapidly perfused tissues capable of eliminating the chemical (e.g., kidneys, lungs, and liver). Compartmental pharmacokinetic models require no information on tissue physiology or anatomical structure, and they are valuable in predicting the plasma chemical concentrations at different doses, establishing the time course of chemical in plasma and tissues and the extent of chemical accumulation with multiple doses, and determining effective dose and dose regimens in toxicity studies.

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Regards

Mary Wilson

Editorial office

Clinical Pharmacology and Toxicology Research

E-mail: pharmatoxicol@eclinicalsci.com