Liver Drug Metabolism

Liver drug metabolism is the set of enzymatic and transport processes that chemically modify medicines, helping regulate their activity, duration, and elimination from the body. In hepatocytes, phase I reactions, often mediated by cytochrome P450 enzymes, introduce or expose functional groups through oxidation, reduction, or hydrolysis, while phase II reactions attach polar molecules such as glucuronide or sulfate to improve water solubility; transporters then support biliary or blood-based clearance. In clinical practice, these processes influence drug dosing, therapeutic response, toxicity, and interactions between medicines. Understanding metabolic pathways also supports safer drug development and individualized treatment decisions.

Liver Drug Metabolism - Related Videos

Research

JoVE Journal - Medicine

Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis

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Cited by 1 •

2025

Mouse model of metabolic dysfunction-associated steatotic liver disease (MASLD) with metabolic dysfunction, hepatic gene expression changes, and liver histopathological alterations that resemble human MASLD, including fibrosis that progresses to advanced fibrosis stage 3. This model can be used in studies of MASLD pathophysiology and in pre-clinical studies of new therapies.

Advancements in the Metabolic Profiling of Three-Dimensional Brain Tumor Spheroids for Drug Screening

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Cited by 1 •

2025

Here, we establish a metabolic profiling platform integrating three-dimensional (3D) glioma spheroids and imaging-based normalization via extracellular flux analysis. This approach enables more accurate assessment of tumor metabolic responses to drug treatments and provides insights into potential mechanisms of resistance.

Education

JoVE Core - Pharmacology

Drug Metabolism: Phase I Reactions

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2023

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...

Drug Metabolism: Phase II Reactions

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2023

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...

Pharmacogenetics of Drug Metabolism: Overview

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2026

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...

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