{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:26:23Z","timestamp":1780680383694,"version":"3.54.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Therapeutic drug monitoring (TDM) of methotrexate (MTX) is challenging due to its pharmacokinetics and short plasma half-life. Intracellular MTX\u2013polyglutamates (PG1\u20135), which accumulate over time, have not been assessed in pediatric inflammatory bowel disease (IBD). This study aimed to evaluate erythrocyte MTX-PG as a potential TDM tool in pediatric IBD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this cross-sectional study, MTX-PG concentrations were measured in erythrocytes of children with IBD on stable low-dose MTX for at least 12 weeks using stable-isotope dilution liquid chromatography\u2013tandem mass spectrometry. The influence of administration route, MTX dosage, and anthropometrics on MTX-PG concentrations was examined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventy-eight patients were included, showing MTX-PG3 as the predominant subspecies (median 27.0 nmol\/L) with a median MTX-PGtotal of 74.8 nmol\/L. A higher MTX dose correlated significantly with elevated levels of MTX-PG3, MTX-PG4, MTX-PG5, and MTX-PGtotal (P\u2005&amp;lt;\u2005.01). Adjusted for body surface area, MTX dose remained significantly associated with higher MTX-PG concentrations (P\u2005&amp;lt;\u2005.01). However, comparison by administration route was limited due to a few patients on subcutaneous MTX (n\u2005=\u20054).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We observed high interindividual variability in the reached erythrocyte MTX-PG concentrations. Body surface adjusted or unadjusted MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in children with IBD. This is a prerequisite for TDM and provides a strong basis for further research into the relation between TDM of MTX, efficacy, and toxicity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izaf035","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:28:32Z","timestamp":1740137312000},"page":"2503-2510","source":"Crossref","is-referenced-by-count":3,"title":["Erythrocyte Methotrexate\u2013Polyglutamate Concentrations in Pediatric Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4335-0100","authenticated-orcid":false,"given":"Eva","family":"Vermeer","sequence":"first","affiliation":[{"name":"Department of Paediatric Gastroenterology, Emma Children\u2019s Hospital, Amsterdam University Medical Centre , Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam University Medical Centre , 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Research Institute, Amsterdam University Medical Centre , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1053-7739","authenticated-orcid":false,"given":"Maja","family":"Bulatovi\u0107-\u0106alasan","sequence":"additional","affiliation":[{"name":"Laboratory of Specialised Diagnostics and Research, Department of Laboratory Medicine, Amsterdam University Medical Centre , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7556-5896","authenticated-orcid":false,"given":"Tim G J","family":"de 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