BIOTRANSFORMATION: THE IMPACT OF THE LIVER ON DRUG METABOLISM
Keywords:
biotransformation, liver metabolism, cytochrome P450, drug metabolism, hepatocytes, Phase I reactions, Phase II reactions, xenobiotics, pharmacokinetics, hepatic clearanceAbstract
This article examines the biochemical, physiological, and clinical aspects of hepatic biotransformation and its fundamental role in drug metabolism. It analyzes the structural and functional organization of hepatocytes, mechanisms of Phase I and Phase II metabolic reactions, the influence of enzymatic variability, genetic factors, pathological conditions, and drug–drug interactions on hepatic metabolism. The article also explores the significance of the cytochrome P450 system, conjugation pathways, plasma protein binding, and hepatic transporters. Moreover, the paper discusses the clinical implications of impaired liver function, dose adjustment strategies, and modern approaches to predicting metabolic pathways through pharmacokinetic modeling. Special attention is given to the integration of biotransformation studies in personalized medicine and drug development. The analysis demonstrates that the liver remains the central organ responsible for chemical transformation of xenobiotics, thereby determining the efficacy, safety, and pharmacokinetic profile of therapeutic agents.
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