Toxicokinetics and Safety Ratios

Pharmacokinetics is essentially the study of “how a substance gets into the body and what happens to it in the body.” Similarly, toxicokinetics deals with what the body does with a drug or other substance when given a relatively high dose relative to the therapeutic dose. Toxicokinetic studies are generally carried out at much higher doses than those used in pharmacokinetic studies, and this dose information is critical for predicting the safety of substances. The primary objective of toxicokinetics is to describe the systemic exposure achieved in animals and its relationship to dose level and the time course of the toxicity study. The ratio of drug exposure in animals at the no observed adverse effect level (NOAEL) and in humans at the expected therapeutic dose is one of the precautionary principles to determine the risk benefit profile of pharmaceuticals.