Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non-target red blood cells of patients with Crohn's disease.
Basic Clin Pharmacol Toxicol
; 135(3): 308-320, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38973551
ABSTRACT
BACKGROUND:
Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG3 concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX-PGs accumulation in peripheral blood mononuclear cells (PBMCs effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker.METHODS:
In a multicentre prospective cohort study, blood samples of patients with CD were collected during the first year of MTX therapy. Mucosal biopsies were obtained from non-inflamed rectum and/or inflamed intestine. MTX-PGs concentrations in mucosa, PBMCs and RBCs were measured by liquid chromatography-tandem mass spectrometry.RESULTS:
From 80 patients with CD, a total of 27 mucosal biopsies, 9 PBMC and 212 RBC samples were collected. From 12 weeks of MTX therapy onwards, MTX-PG3 was the most predominant species (33%) in RBCs. In PBMCs, the distribution was skewed towards MTX-PG1 (48%), which accounted for an 18 times higher concentration than in RBCs. Long-chain MTX-PGs were highly present in mucosa 21% of MTX-PGtotal was MTX-PG5. MTX-PG6 was measurable in all biopsies.CONCLUSIONS:
MTX-PG patterns differ between mucosa, PBMCs and RBCs of patients with CD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Crohn Disease
/
Methotrexate
/
Erythrocytes
/
Intestinal Mucosa
Limits:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Basic Clin Pharmacol Toxicol
/
Basic and clinical pharmacology and toxicology
/
Basic clin. pharmacol. toxicol
Journal subject:
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Países Bajos
Country of publication:
Reino Unido