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Novel assay to improve therapeutic drug monitoring of thiopurines in inflammatory bowel disease
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Skåne University Hospital, Sweden; Danderyd Hospital, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
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2014 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 12, 1702-1709 p.Article in journal (Refereed) Published
Abstract [en]

Background and aims: The thiopurines are widely used in the treatment of inflammatory bowel disease, but are limited by poor dose effect relationship. The objective was to assess the ability of a novel assay, determining the mono-, di-, and triphosphates, of thioguanine as well as methylthioinosine as individual metabolites in erythrocytes, to predict clinical outcome compared to a routine assay, determining metabolites as sums. Methods: Samples from 79 patients with Crohns disease or ulcerative colitis treated with azathioprine or mercaptopurine were analysed by both assays. Clinical status was determined by the Harvey-Bradshaw and Walmsley indices. The genotypes of thiopurine methyltransferase (TPMT) and inosine triphosphatase were determined. Results: TPMT wild-type patients with thioguanine nucleotide (TGN) levels below the cut-off level were more likely to have active disease when TGN was measured by the novel assay (p = 0.02), and when thioguanosine triphosphate (TGTP) was measured separately (p = 0.01). When TGN was measured by the routine assay the correlation was not evident (p = 0.12). Neither TGN levels nor TGTP correlated to disease activity in TPMT deficient patients. Patients with methyl thioinosine nucleotide (meTIN) levels above 1500 pmol/8 x 10less than^greater than8 RBCs were more likely to have active disease (p = 0.07). We observed good correlations between the mono-, di-, and triphosphates and their respective sums (R-2 greater than 0.88). Conclusions: The novel TGN assay was better in predicting clinical outcome compared to the routine assay, while determination of TGTP had no clinical advantage and TGTP ratio was not correlated to disease activity. (C) 2014 European Crohns and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier , 2014. Vol. 8, no 12, 1702-1709 p.
Keyword [en]
Purines; HPLC; Inflammatory bowel diseases; Individualized medicine; Thiopurine; Azathioprine
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-113783DOI: 10.1016/j.crohns.2014.08.009ISI: 000347019600016PubMedID: 25239576OAI: oai:DiVA.org:liu-113783DiVA: diva2:785156
Note

Funding Agencies|Medical Research Council of Southeast Sweden (FORSS) [FORSS-161041, FORSS-235971]; Swedish Society of Medicine [SLS-178771]; County Council of Ostergotland [LIO 130231, LIO 207561, LIO 284811]; Swedish Cancer Society [CAN 2011/401]; Swedish Childhood Cancer Foundation (BCF) [12/052]; Ruth and Richard Julin Foundation; Swedish Research Council [2008-4035]

Available from: 2015-02-02 Created: 2015-01-30 Last updated: 2017-12-05

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Vikingsson, SvanteAlmer, SvenPeterson, Curt

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