Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease

Monika Fischer, Shivi Siva, Gwendolyn K. Cook, David R. Jones, Hala M. Fadda

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlun) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlun levels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlun) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu3+4+5) concentrations compared with those with active disease, a definitive association between RBC MTXGlu3+4+5 levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlun levels as indicators of treatment efficacy and clinical outcome.

Original languageEnglish (US)
JournalClinical Pharmacology in Drug Development
DOIs
StateAccepted/In press - 2016

Fingerprint

Physiologic Monitoring
Crohn Disease
Methotrexate
Erythrocytes
Glutamic Acid
Remission Induction
Immunosuppressive Agents
methotrexate polyglutamate
Longitudinal Studies
Mass Spectrometry
Cross-Sectional Studies
High Pressure Liquid Chromatography
Maintenance

Keywords

  • Bioavailability
  • Immunosuppressant
  • Inflammatory bowel disease
  • Methotrexate polyglutamate
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease. / Fischer, Monika; Siva, Shivi; Cook, Gwendolyn K.; Jones, David R.; Fadda, Hala M.

In: Clinical Pharmacology in Drug Development, 2016.

Research output: Contribution to journalArticle

Fischer, Monika ; Siva, Shivi ; Cook, Gwendolyn K. ; Jones, David R. ; Fadda, Hala M. / Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease. In: Clinical Pharmacology in Drug Development. 2016.
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