Related Experiment Video

Updated: Feb 15, 2026

Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
08:32

Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice

Published on: March 10, 2017

10.6K

ITPA Activity in Children Treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and

Antony Citterio-Quentin1,2, Mustapha Moulsma2, Marie-Paule Gustin3

  • 1UMR CNRS 5305, Clinical Pharmacy, Pharmacokinetics and Drug Evaluation, Université de Lyon, Université Lyon 1, Lyon, France.

Basic & Clinical Pharmacology & Toxicology
|January 13, 2018
PubMed

Insights

Inosine triphosphate pyrophosphatase (ITPA) activity in children on azathioprine (AZA) therapy was not linked to adverse drug reactions. However, high ITPA activity correlated with inflammation markers in pediatric inflammatory bowel disease (IBD) patients.

Area of Science:

  • Pharmacogenomics
  • Pediatric Immunology
  • Drug Metabolism

Background:

  • Azathioprine (AZA), a thiopurine drug, is essential for treating pediatric immunological diseases like inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH).
  • Significant inter-individual variability exists in AZA's adverse drug reactions (ADRs) and treatment efficacy.
  • Inosine triphosphate pyrophosphatase (ITPA) plays a role in thiopurine metabolism, potentially influencing AZA's effects.

Purpose of the Study:

  • To investigate the relationship between ITPA enzyme activity and ADRs in children with immunological diseases receiving AZA.
  • To explore the association between ITPA activity and inflammatory markers in pediatric patients diagnosed with IBD.

Main Methods:

  • ITPA and thiopurine S-methyltransferase (TPMT) activities were measured in 106 children undergoing AZA therapy for immunological conditions.
  • Retrospective collection of clinical data, including markers for hepatotoxicity, myelotoxicity, pancreatitis, and inflammation.
  • Statistical analysis to determine correlations between ITPA activity and ADRs, and between ITPA activity and inflammatory markers in IBD patients.

Main Results:

  • No significant association was found between ITPA activity and hepatotoxicity or common clinical ADRs (e.g., skin reactions, arthralgia, gastrointestinal issues).
  • A significant correlation was observed between ITPA activity and red blood cell (RBC) mean corpuscular volume (MCV), a marker of myelotoxicity (p=0.003).
  • High ITPA activity showed a significant relationship with elevated gamma-globulin levels, an indicator of inflammation, in children with IBD (p=0.005).

Conclusions:

  • ITPA activity was not directly associated with the occurrence of ADRs in pediatric patients on AZA therapy.
  • A notable link between high ITPA activity and increased inflammation markers (gamma-globulin) was identified in pediatric IBD patients.
  • Measuring ITPA activity may aid in identifying pediatric IBD patients at risk for persistent inflammation despite AZA treatment, warranting further prospective research.

More Related Videos

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response12:50

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

7.0K
Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization09:57

Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization

Published on: September 20, 2024

3.6K

Related Concept Videos

Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.8K
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
17.1K
Inflammatory Response II: Inflammatory Exudate and Tissue Repair01:24

Inflammatory Response II: Inflammatory Exudate and Tissue Repair

The immune system's inflammatory response destroys the invading pathogen, permitting the tissue to heal. The changes during the cellular and vascular stages allow exudate formation at the site of inflammation. The inflammatory exudate released from the wound has high protein content and a specific gravity above 1.020.
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...
8.1K
Dose-Response Relationship: Overview01:03

Dose-Response Relationship: Overview

Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
5.2K
Inflammatory Response I: Vascular and Cellular01:30

Inflammatory Response I: Vascular and Cellular

The inflammatory response is the body's defense against infection, injury, or irritation from bacteria, trauma, toxins, or heat. Inflammation helps locate and destroy pathogens and remove damaged tissue elements to heal the body. During this initial phase, fluid, blood products, and nutrients migrate to the injured area, resulting in redness, heat, swelling, ache, and loss of function. Moreover, signs of systemic inflammation include fever, increased WBC count, malaise, anorexia, nausea,...
16.9K
Drug Dosing: Infants and Children01:29

Drug Dosing: Infants and Children

Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
335