ABSTRACT
Many of the drugs, poisons, toxins, or other exogenous compounds that enter the body are chemically modi-ed prior to their eventual elimination. ese structural changes oen facilitate or hasten the removal of chemicals from the body by making them more water soluble, and therefore more readily subject to elimination in the urine. In many cases, the structural changes serve to make the compound less toxic, such as the hydrolysis of the methyl ester of cocaine to form benzoylecgonine, or the attachment of a glucuronic acyl residue to morphine, yielding morphine glucuronide. In some cases, however, the metabolic product is actually more toxic than the original molecule, such as the formation of a toxic quinone-imine metabolite from acetaminophen
(NAPQI; N-acetyl para-quinonimine), which can damage the liver and kidney, or formic acid from methanol, to which the optic nerve is particularly sensitive. Chemical changes that produce more toxic species are called activation reactions; those that render compounds less toxic are considered to be deactivation reactions. While metabolic transformations can occur throughout the body, much of the breakdown of xenobiotics takes place in the liver. In a general sense, the purpose of metabolic transformations can be thought of as twofold: to decrease the toxicity of exogenous compounds, and to enhance their aqueous solubility (thereby shortening their residence time in the body). Knowledge of the metabolic fate of a drug in the body can help the toxicologist evaluate and understand the signicance of their analytical ndings in the overall context of a case.
