Toxicophores: groups and metabolic routes associated with increased safety risk

Drugs and chemicals can be metabolized in living organisms in an effort to remove them from the body. During this excretion process, certain chemicals can be transformed into unstable, highly reactive species. This can result in the overwhelming of cellular defense, allowing the reactive metabolite to bind to cellular macromolecules, and leading to abnormal cellular function. It is widely accepted that this process can lead to clinically observed toxicities in the form of idiosyncratic adverse drug reactions. However, it is currently impossible to predict which chemical species will cause these reactions. This review focuses on drugs from which reactive metabolites have been detected and reiterates the need for a more thorough understanding of basic drug metabolism before attempting to relate chemical species formation to biological function.