Bioactivation and reactivity research advances - 2023 year in review.
Shuai WangUpendra A ArgikarMaria ChatzopoulouSungjoon ChoRachel D CrouchDeepika DhawareTing-Jia GuCarley J S HeckKevin M JohnsonAmit S KalgutkarJoyce LiuBin MaGrover P MillerJessica A RowleyHerana Kamal SeneviratneDonglu ZhangS Cyrus KhojastehPublished in: Drug metabolism reviews (2024)
Advances in the field of bioactivation have significantly contributed to our understanding and prediction of drug-induced liver injury (DILI). It has been established that many adverse drug reactions, including DILI, are associated with the formation and reactivity of metabolites. Modern methods allow us to detect and characterize these reactive metabolites in earlier stages of drug development, which helps anticipate and circumvent the potential for DILI. Improved in silico models and experimental techniques that better reflect in vivo environments are enhancing predictive capabilities for DILI risk. Further, studies on the mechanisms of bioactivation, including enzyme interactions and the role of individual genetic differences, have provided valuable insights for drug optimizations. Cumulatively, this progress is continually refining our approaches to drug safety evaluation and personalized medicine.