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Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
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Erythrocyte Methotrexate-Polyglutamate Concentrations in Pediatric Inflammatory Bowel Disease

Eva Vermeer1,2,3, Eduard A Struys4, Marry Lin4

  • 1Department of Paediatric Gastroenterology, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands.

Inflammatory Bowel Diseases
|February 21, 2025
PubMed
Abstract

Insights

Erythrocyte methotrexate-polyglutamates (MTX-PG) show promise for therapeutic drug monitoring (TDM) in pediatric inflammatory bowel disease (IBD). Higher MTX doses correlate with increased MTX-PG levels, supporting their use in TDM.

Area of Science:

  • Pharmacology
  • Pediatric Gastroenterology
  • Analytical Chemistry

Background:

  • Therapeutic drug monitoring (TDM) of methotrexate (MTX) is challenging due to its pharmacokinetics.
  • Intracellular MTX-polyglutamates (MTX-PG) have not been assessed in pediatric inflammatory bowel disease (IBD).

Purpose of the Study:

  • Evaluate erythrocyte MTX-PG as a potential TDM tool in pediatric IBD.
  • Assess the influence of MTX dosage, administration route, and anthropometrics on MTX-PG concentrations.

Main Methods:

  • Cross-sectional study of 78 children with IBD on stable low-dose MTX.
  • Measured erythrocyte MTX-PG concentrations using stable-isotope dilution liquid chromatography-tandem mass spectrometry.
  • Examined correlation between MTX dosage, administration route, anthropometrics, and MTX-PG levels.

Main Results:

  • MTX-PG3 was the predominant subspecies, with MTX-PGtotal median of 74.8 nmol/L.
  • Higher MTX doses significantly correlated with elevated MTX-PG3, MTX-PG4, MTX-PG5, and MTX-PGtotal (P < .01).
  • MTX dose remained significantly associated with higher MTX-PG concentrations after adjusting for body surface area (P < .01).

Conclusions:

  • High interindividual variability in erythrocyte MTX-PG concentrations was observed.
  • MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in pediatric IBD.
  • Erythrocyte MTX-PG concentrations are a prerequisite for TDM, supporting further research on MTX efficacy and toxicity.
Keywords:
Crohn’s diseasemethotrexatepediatric inflammatory bowel diseasetherapeutic drug monitoringulcerative colitis

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