Related Experiment Video

Updated: Aug 11, 2026

Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
07:05

Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis

Published on: May 12, 2019

[Comparison of gastrointestinal toxicity of 5-FU derivatives]

I Imamura1, M Yabumoto, H Fukui

  • 1Dept. of Pharmacology II, Faculty of Medicine, Osaka University.

Gan to Kagaku Ryoho. Cancer & Chemotherapy
|July 1, 1993
PubMed

Insights

Doxifluridine (DFUR) causes greater gastrointestinal toxicity than tegafur (FT) due to faster metabolism and higher 5-fluorouracil (5-FU) formation in the gut. This explains the increased incidence of diarrhea observed with DFUR treatment.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Drug Metabolism

Background:

  • Tegafur (FT) and doxifluridine (DFUR) are 5-fluorouracil (5-FU) prodrugs used in cancer therapy.
  • Gastrointestinal (GI) toxicities are common side effects of these chemotherapeutic agents.
  • Understanding the differential toxicity profiles is crucial for optimizing patient treatment.

Purpose of the Study:

  • To compare the gastrointestinal toxicities of tegafur (FT) and doxifluridine (DFUR).
  • To investigate the relationship between drug metabolism, 5-FU formation, and observed toxicities.

Main Methods:

  • Comparison of enzyme activities in mouse intestinal tissues after repeated administration of FT and DFUR.
  • Pharmacokinetic analysis to assess drug catabolism rates.
  • In vitro assessment of 5-FU generation from FT and DFUR using gastrointestinal extracts.

Main Results:

  • Repeated administration of both FT and DFUR decreased intestinal enzyme activities.
  • DFUR administration, especially twice daily, led to a greater decrease in enzyme activity compared to FT.
  • Pharmacokinetic studies indicated faster catabolism of DFUR than FT.
  • In vitro studies showed significantly higher 5-FU formation from DFUR compared to FT in GI extracts.

Conclusions:

  • DFUR exhibits greater gastrointestinal toxicity than FT, evidenced by reduced intestinal enzyme activity.
  • Faster DFUR metabolism and increased in vitro 5-FU generation correlate with higher toxicity.
  • These findings explain the higher incidence of diarrhea associated with DFUR treatment.

More Related Videos

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform06:21

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

Related Concept Videos

Drugs for Treatment of Ulcerative Colitis in IBD01:29

Drugs for Treatment of Ulcerative Colitis in IBD

Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide generation. 
Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence01:22

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Drug Toxicity: Overview01:00

Drug Toxicity: Overview

Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...