Modulating UDP-glucuronosyltransferase activity: Mechanisms, clinical implications, therapeutic strategies, and...

UDP-glucuronosyltransferases (UGTs) are essential enzymes in the phase II metabolism of endogenous and exogenous compounds, playing a critical role in detoxification, drug metabolism, and clearance. Their function is crucial for the pharmacokinetics of numerous therapeutic agents, but UGT inhibition can result in altered drug metabolism, increased toxicity, or reduced efficacy. This review explores the mechanisms of UGT inhibition, its implications for drug metabolism and pharmacokinetics, and the clinical relevance of such inhibition in the context of drug-drug interactions (DDIs). We discuss the therapeutic strategies targeting UGTs, the impact of environmental and dietary factors on UGT activity, and the role of pharmacogenetics in modulating UGT function. Moreover, the review highlights the role of UGTs in xenobiotic detoxification and addresses the challenges in identifying and modulating UGT inhibition in drug development. Finally, we identify future research directions for understanding UGT inhibition and its clinical applications. By synthesizing recent advances in the field, this review provides a comprehensive overview of the dynamic role of UGTs in drug metabolism, offering insights for optimizing drug therapy and minimizing adverse interactions.