{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:11:31Z","timestamp":1758874291452,"version":"3.44.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Shunting (hypermethylating) thiopurine metabolism, characterized by excessive 6\u2010MMPR production and (sub)therapeutic 6\u2010TGN levels, poses a significant challenge in the treatment of inflammatory bowel disease (IBD). This study evaluates the metabolic outcomes of switching to low\u2010dose thiopurine with allopurinol (LDTA) or thioguanine (TG) in IBD patients with shunting metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective study analysed demographic data, thiopurine metabolite profiles, and adverse event rates in shunting IBD patients before and after switching to LDTA or TG therapy. Metabolite variability was assessed by examining alterations in 6\u2010MMPR and 6\u2010TGN levels and their correlation before and after therapy switch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both therapies significantly reduced toxic 6\u2010MMPR levels, with 100% of patients achieving non\u2010toxic levels (6\u2010MMPR\u2010level below 7000\u2009pmol\/8\u2009\u00d7\u200910E8 RBC) post\u2010therapy. For TG, 93% of patients attained non\u2010toxic 6\u2010TGN levels (6\u2010TGN\u2009&lt;\u20091000\u2009pmol\/8\u2009\u00d7\u200910E8 RBC). In contrast, LDTA showed greater variability in 6\u2010TGN outcomes, with 50% of patients reaching therapeutic levels, 31% remaining subtherapeutic, and 19% within toxic range. The slope for LDTA was significantly positive (1.044, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.4515, <jats:italic>P<\/jats:italic>\u2009=\u20090.004), reflecting proportional increases in 6\u2010TGN levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Switching to LDTA or TG therapy in shunting IBD patients resulted in favourable alterations in thiopurine metabolism. However, LDTA appears to have a slightly less favourable metabolite profile, with some residual 6\u2010MMPR formation and fewer patients achieving normal 6\u2010TGN levels compared to TG. Given the challenges associated with achieving optimal thiopurine metabolite levels with LDTA and the need for closer monitoring of 6\u2010TGN levels, TG appears a more suitable option for thiopurine shunting IBD patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70112","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T06:22:30Z","timestamp":1748326950000},"page":"2865-2873","source":"Crossref","is-referenced-by-count":0,"title":["The fate of thiopurine metabolites after switching to low\u2010dose thiopurine with allopurinol or thioguanine in IBD patients: A retrospective analysis"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-9312","authenticated-orcid":false,"given":"Ahmed B.","family":"Bayoumy","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute  Amsterdam The Netherlands"},{"name":"Department of Clinical Pharmacy and Pharmacology M\u00e1xima Medical Center  Veldhoven The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hedwig M. A.","family":"D'Agnolo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology M\u00e1xima Medical Center  Veldhoven The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanne K. H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris J. J.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc J. J.","family":"Derijks","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology M\u00e1xima Medical Center  Veldhoven The Netherlands"},{"name":"Department of Clinical Pharmacy and Toxicology and NUTRIM, School of Nutrition and Translational Research in Metabolism Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2020.00155"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000169061.52715.3e"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izx081"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2012.05084.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2067"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13656"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620\u2010022\u201007719\u2010x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2009.04221.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20102952(66)90163\u20108"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumd00512\u20100010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328334338f"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12664\u2010024\u201001529\u2010x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjad013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101332"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15730"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2012.05206.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro\u20102016\u2010100738"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102023\u2010329679"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31464"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378\u20104347(92)80347\u2010S"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691\u2010200406000\u201000016"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.11.008"},{"issue":"1","key":"e_1_2_10_24_1","first-page":"S1","article-title":"The concise guide to pharmacology 2021\/22: introduction and other protein targets","volume":"178","author":"Alexander SP","year":"2021","journal-title":"Br J Pharmacol"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001131"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00054725\u2010200108000\u201000001"},{"key":"e_1_2_10_27_1","first-page":"13","article-title":"Position paper on the use of drug therapies in the management of inflammatory bowel disease","volume":"19","author":"Watermeyer G","year":"2021","journal-title":"S Afr Gastroenterol Rev"},{"key":"e_1_2_10_28_1","first-page":"20","article-title":"Second BRAZILIAN consensus on the management of CROHN'S disease in adults: a consensus of the BRAZILIAN organization for CROHN'S disease and colitis (GEDIIB)","volume":"59","author":"Imbrizi M","year":"2023","journal-title":"Arq Gastroenterol"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rgmx.2016.07.003"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T07:31:20Z","timestamp":1758871880000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/bcp.70112"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70112","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"type":"print","value":"0306-5251"},{"type":"electronic","value":"1365-2125"}],"subject":[],"published":{"date-parts":[[2025,5,27]]}}}