ABSTRACT
Pharmacokinetics is the quantitative study of factors that control the time course for absorption, distribution, metabolism, and excretion of chemicals within the body. Pharmacokinetic (PK) models provide sets of equations that simulate the time courses of chemicals and their metabolites in various tissues throughout the body. The interest in PK modeling in toxicology arose from the need to relate internal concentrations of active compounds at their target sites with the doses of chemical given to an animal or human subject. The reason, of course, is a fundamental tenet in toxicology that both benecial and adverse responses to compounds are related to the concentrations of active chemicals reaching target tissues rather than the amounts of chemical at the site of absorption. The relationships between tissue dose and administered dose can be complex, especially in high dose toxicity testing studies, with multiple, repeated daily dosing, or when metabolism or toxicity at routes of entry alters uptake processes for various routes of exposure. PK models of all kinds are primarily a tool to assess chemical dosimetry at target tissues for a wide range of exposure situations.
