{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:49:42Z","timestamp":1777294182491,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008695","name":"Japan Foundation for Applied Enzymology","doi-asserted-by":"publisher","award":["18S006"],"award-info":[{"award-number":["18S006"]}],"id":[{"id":"10.13039\/100008695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Thiopurines are often used in combination with mesalazine for the treatment of ulcerative colitis (UC). Mesalazine formulations are delivered to the digestive tract by various delivery systems and absorbed as 5\u2010aminosalicylic acid (5\u2010ASA). 5\u2010ASA is known to inhibit thiopurine <jats:italic>S<\/jats:italic>\u2010methyltransferase (TPMT) activity and to affect thiopurine metabolism. There have been no studies comparing TPMT inhibition by multimatrix mesalazine (MMX) with other formulations. We investigated the difference in TPMT inhibition by different mesalazine formulations and prospectively confirmed the clinical relevance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma concentrations of 5\u2010ASA, <jats:italic>N<\/jats:italic>\u2010acetyl\u20105\u2010aminosalicylic acid (<jats:italic>N<\/jats:italic>\u2010Ac\u20105\u2010ASA), and TPMT activities were measured in UC patients receiving various mesalazine formulations (time\u2010dependent or pH\u2010dependent mesalazine or MMX) as monotherapy. Patients already on both time\u2010dependent or pH\u2010dependent mesalazine and thiopurines switched their mesalazine to MMX, examining 6\u2010thioguanine nucleotide (6\u2010TGN) and 6\u2010methylmercaptopurine (6\u2010MMP) 0 and 8\u00a0weeks after switching. Clinical relapse after switching was also monitored for 24\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma 5\u2010ASA and <jats:italic>N<\/jats:italic>\u2010Ac\u20105\u2010ASA levels were significantly higher in patients receiving time\u2010dependent mesalazine (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) compared with pH\u2010dependent mesalazine (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) and MMX (<jats:italic>n<\/jats:italic>\u00a0=\u00a015), accompanied by greater TPMT inhibition. Prospective switching from time\u2010dependent mesalazine to MMX decreased 6\u2010TGN levels, increased those of 6\u2010MMP, and increased 6\u2010MMP\/6\u2010TGN ratios. Furthermore, this resulted in significantly more relapses than switching from pH\u2010dependent mesalazine to MMX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Time\u2010dependent mesalazine has higher plasma 5\u2010ASA and <jats:italic>N<\/jats:italic>\u2010Ac\u20105\u2010ASA levels and greater TPMT inhibition than MMX. Therefore, switching from time\u2010dependent mesalazine to MMX may lead to an increase of 6\u2010MMP\/6\u2010TGN, which may reduce the clinical effectiveness of thiopurines, warranting close monitoring after switch.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15411","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T14:38:24Z","timestamp":1611153504000},"page":"2116-2124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Differential effects of mesalazine formulations on thiopurine metabolism through thiopurine S\u2010methyltransferase inhibition"],"prefix":"10.1111","volume":"36","author":[{"given":"Hiromu","family":"Morikubo","sequence":"first","affiliation":[{"name":"Center for Advanced IBD Research and Treatment Kitasato University Kitasato Institute Hospital  Tokyo Japan"},{"name":"Department of Gastroenterology and Hepatology Kitasato University Kitasato Institute Hospital  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University Kitasato Institute Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kuronuma","sequence":"additional","affiliation":[{"name":"Department of Research, BioMedical Laboratory Kitasato University Kitasato Institute Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Research, BioMedical Laboratory Kitasato University Kitasato Institute Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tenyo","family":"Shiba","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacy, Research and Education Center for Clinical Pharmacy, School of Pharmacy Kitasato University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kiyohara","sequence":"additional","affiliation":[{"name":"Center for Advanced IBD Research and 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