{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:08:54Z","timestamp":1784099334014,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020098","name":"Innovative Health Initiative","doi-asserted-by":"publisher","award":["101194780"],"award-info":[{"award-number":["101194780"]}],"id":[{"id":"10.13039\/100020098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018696","name":"HORIZON EUROPE Health","doi-asserted-by":"publisher","award":["101095470"],"award-info":[{"award-number":["101095470"]}],"id":[{"id":"10.13039\/100018696","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018696","name":"HORIZON EUROPE Health","doi-asserted-by":"publisher","award":["101136582"],"award-info":[{"award-number":["101136582"]}],"id":[{"id":"10.13039\/100018696","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["452022317"],"award-info":[{"award-number":["452022317"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thiopurines are used to maintain remission in inflammatory bowel disease (IBD). These drugs are metabolized into 6\u2010thioguanine nucleotides (6\u2010TGN), associated with efficacy, and 6\u2010methylmercaptopurine ribonucleotides (6\u2010MMPR), associated with adverse drug reactions. Pregnancy has been linked to a shift in thiopurine metabolism, characterized by reduced 6\u2010TGN and increased 6\u2010MMPR levels. The clinical impact of these changes remains unclear. To explore the association between changes in 6\u2010TGN and 6\u2010MMPR levels with disease activity and toxicity markers in women with IBD during pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included pregnant women with IBD who used thiopurines from six Dutch hospitals (2017\u20132022). Linear mixed\u2010effects models were used to model changes of 6\u2010TGN and 6\u2010MMPR before, during and after pregnancy, and to identify associations with markers of disease activity (faecal calprotectin) and toxicity (alanine aminotransferase [ALT], leukocytes, platelets).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 87 women with 100 pregnancies were included (64.4% Crohn's disease, 32.2% ulcerative colitis). A significant reduction in 6\u2010TGN was found in the second and third trimester, but no associations with changes in faecal calprotectin were detected. There were no significant increases in 6\u2010MMPR. Increases in 6\u2010MMPR were associated with modest elevations in ALT, but none of the other toxicity markers. Transient thrombocytopenia and leukopenia occurred thrice, and elevated liver enzymes were observed in nine pregnancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although 6\u2010TGN levels decreased during pregnancy, these fluctuations were not associated with increased disease activity or toxicity. No significant increase in 6\u2010MMPR levels was observed. Proactive monitoring may therefore not be warranted in the pregnant population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70520","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:52:12Z","timestamp":1773820332000},"page":"2364-2376","source":"Crossref","is-referenced-by-count":0,"title":["The decline of 6\u2010thioguanine nucleotides is not linked to impaired efficacy or safety of thiopurines in pregnant women with inflammatory bowel disease"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6208-2967","authenticated-orcid":false,"given":"Dianne G.","family":"Bouwknegt","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3551-1201","authenticated-orcid":false,"given":"Paola","family":"Mian","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"van den Berg\u2010Zuiddam","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Leiden University Medical Center, Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea E.","family":"van der Meulen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Leiden University Medical Center, Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Crouwel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam University Medical Center, University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanne K.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam University Medical Center, University of Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute Amsterdam University Medical Center  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-5713","authenticated-orcid":false,"given":"Debbie S.","family":"Deben","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Pharmacology &amp; Toxicology Zuyderland Medical Center  Sittard\u2010Geleen\/Heerlen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Pharmacology &amp; Toxicology Zuyderland Medical Center  Sittard\u2010Geleen\/Heerlen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J. 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