Enzyme Induction and Drug Metabolism

Abstract

Enzyme induction is one of the most important underlying mechanism of drug-drug interactions (DDIs). It can be defined as an increase in the biosynthesis of metabolizing enzymes after the exposure of the organism to environmental factors (e.g., chemical agents such as drugs or pollutants) or due to physiological/pathophysiological conditions (e.g., hormone or cytokine release). It is mediated by increased transcription of mRNA encoding the genes for drug-metabolizing enzymes; the augmented enzyme levels lead to the increase of the maximum reaction velocity Vmax, which in turn results in a diminished exposure to the parent drug and an increased exposure to the drug metabolite(s) produced by the induced enzyme (or by subsequent metabolizing steps in the same metabolic pathway). The result can be either a decrease or an increase in the pharmacological effect of the drug, depending upon whether the parent drug or its metabolite is the active entity, respectively.