THE ROLE OF ACTIVE METABOLITES IN DRUG TOXICITY

Adverse drug reactions can be caused by the parent drug or a metabolit e of that drug. The metabolite may be stable or chemically reactive, t he resultant toxicity being either a direct extension of the pharmacol ogy of the drug, or unrelated to the known pharmacology of the drug an d dependent on the chemical properties of the compound. Many different organ systems may be affected, and there are several mechanisms invol ved in determining organ-specific, and sometimes cell-selective, toxic ity. An imbalance between bioactivation of a drug to a toxic metabolit e and its detoxification is of prime importance in determining individ ual susceptibility. Such an imbalance may be genetically determined or acquired and, furthermore, may be systemic or tissue-specific. Preven tion of metabolite-mediated toxicity is possible once the mechanism of toxicity has been elucidated.