| Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy. | |
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MedLine Citation:
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PMID: 22398098 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is ≥235pmol/8×10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263pmol/8×10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235pmol/8×10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response. |
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Authors:
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Lennard P L Gilissen; Dennis R Wong; Leopold G J B Engels; Jörgen Bierau; Jaap A Bakker; Aimée D C Paulussen; Mariëlle J Romberg-Camps; Arnold Stronkhorst; Paul Bus; Laurens P Bos; Piet M Hooymans; Reinhold W Stockbrügger; Cees Neef; Ad A M Masclee |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
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Title: Journal of Crohn's & colitis Volume: - ISSN: 1876-4479 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-3-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101318676 Medline TA: J Crohns Colitis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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