Enzyme induction and drug metabolism

ALAN TALEVI; CAROLINA L. BELLERA

The ADME Encyclopedia. A Comprehensive Guide on Biopharmacy and Pharmacokinetics

Springer Nature

Lugar: Basignstoke; Año: 2022; p. 471 - 478

Enzyme induction is one of the most important underlying mechanism of drug-drug interactions. 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) [1-3]. 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.Importantly, the effects of enzyme induction will appear and disappear relatively slowly (in comparison, for instance, with drug-drug interactions emerging from enzyme inhibition). The time course of enzyme induction will depend on the half-life of the inducer as well as on the rates of synthesis and degradation of the induced protein(s). Whereas the present entry focuses on enzyme induction, the same principles described here can be translated to the induction of proteins with a different function, e.g., drug transporters.