Modeling the Bioactivation and Subsequent Reactivity of Drugs.

ABSTRACT: Electrophilically reactive drug metabolites are implicated in many adverse drug reactions. In this mechanism-termed bioactivation-metabolic enzymes convert drugs into reactive metabolites that often conjugate to nucleophilic sites within biological macromolecules like proteins. Toxic metabolite-product adducts induce severe immune responses that can cause sometimes fatal disorders, most commonly in the form of liver injury, blood dyscrasia, or the dermatologic conditions toxic epidermal necrolysis and Stevens-Johnson syndrome. This study models four of the most common metabolic transformations that result in bioactivation: quinone formation, epoxidation, thiophene sulfur-oxidation, and nitroaromatic reduction, by synthesizing models of metabolism and reactivity. First, the metabolism model

SUBMITTER: Hughes TB 

PROVIDER: S-EPMC8716317 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature