{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:34:26Z","timestamp":1768725266082,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Azathioprine (AZA) and 6\u2010mercaptopurine are prescribed in acute lymphoblastic leukaemia (ALL) and inflammatory bowel diseases (IBD). Metabolism to active 6\u2010thioguanine (6TGN) and 6\u2010methylmercaptopurine nucleotides (6MMPN) is variable but therapeutic drug monitoring (TDM) remains debatable. This study reports on factors impacting on red blood cell (RBC) metabolites concentrations in children to facilitate TDM interpretation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The first paediatric TDM samples received during year 2021 were analysed, whatever indication and thiopurine drug. Target concentration ranges were 200\u2013500, &lt;6000\u2009pmol\/8\u00a0\u00d7\u200910<jats:sup>8<\/jats:sup> RBC for 6TGN and 6MMPN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Children (<jats:italic>n<\/jats:italic>\u00a0=\u2009492) had IBD (64.8%), ALL (22.6%) or another autoimmune disease (12.6%): mean ages at TDM were 7.5 in ALL and 13.7\u00a0years in IBD (<jats:italic>P\u2009&lt;<\/jats:italic>\u00a0.0001). ALL received 6\u2010mercaptopurine (mean dose 1.7\u00a0mg\/kg\/d with methotrexate), IBD received AZA (1.9\u00a0mg\/kg\/d with anti\u2010inflammatory drugs and\/or monoclonal antibodies). Median 6TGN and 6MMPN concentrations were 213.7 [interquartile range: 142.5; 309.6] and 1144.6 [419.4; 3574.3] pmol\/8\u00a0\u00d7\u200910<jats:sup>8<\/jats:sup> RBC, 38.8% of patients were in the recommended therapeutic range for both compounds. Aminotransferases and blood tests were abnormal in 57\/260 patients: 8.1% patients had high alanine aminotransaminase, 3.4% of patients had abnormal blood count. Factors associated with increased 6TGN were age at TDM and thiopurine methyltransferase genotype in ALL and AZA dose in IBD. The impact of associated treatment in IBD patients was also significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TDM allowed identification of children who do not reach target levels or remain over treated. Including TDM in follow\u2010up may help physicians to adjust dosage with the aim of reducing adverse effects and improve treatment outcome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15894","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T03:55:01Z","timestamp":1692935701000},"page":"209-219","source":"Crossref","is-referenced-by-count":4,"title":["Key factors associated with 6\u2010thioguanine and 6\u2010methylmercaptopurine nucleotide concentrations in children treated by thiopurine for acute leukaemia and inflammatory bowel disease"],"prefix":"10.1111","volume":"90","author":[{"given":"Tiphaine Adam","family":"de Beaumais","sequence":"first","affiliation":[{"name":"Department of Biological Pharmacology and Pharmacogenetics H\u00f4pital Saint\u2010Louis, Assistance Publique \u2010 H\u00f4pitaux de Paris  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