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Review
. 2016 Nov 6;7(4):524-530.
doi: 10.4292/wjgpt.v7.i4.524.

How I treat my inflammatory bowel disease-patients with thiopurines?

Berrie Meijer  1 , Chris Jj Mulder  1 , Adriaan A van Bodegraven  1 , Nanne K H de Boer  1
Affiliations
Review

How I treat my inflammatory bowel disease-patients with thiopurines?

Berrie Meijer et al. World J Gastrointest Pharmacol Ther. .

Abstract

Thiopurines are essential drugs to maintain remission in patients with inflammatory bowel disease (IBD). Thiopurines used in IBD are azathioprine (2.0-2.5 mg/kg), mercaptopurine (1.0-1.5 mg/kg) and thioguanine (0.2-0.3 mg/kg). However, mainly due to numerous adverse events associated with thiopurine use, almost 50% of the patients have to discontinue conventional thiopurine treatment. Extensive monitoring and the application of several treatment strategies, such as split-dose administration, co-administration with allopurinol or dose reduction/increase, may increase the chance of successful therapy. With this review, we provide practical information on how thiopurines are initiated and maintained in two thiopurine research centers in The Netherlands. We provide clinical information concerning safety issues, indications and management of therapy that may serve as a guide for the administration of thiopurines in IBD patients in daily practice.

Keywords: Azathioprine; Inflammatory bowel disease; Mercaptopurine; Metabolites; Pregnancy; Therapeutic drug monitoring; Thioguanine; Thiopurines.

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Conflict of interest statement

Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.

Figures

Figure 1
Figure 1
Simplified scheme of thiopurine metabolism. Azathioprine is converted to mercaptopurine by the enzyme glutathione S-transferase (GST), by separating the imidazole-group. 6-Mercaptopurine is enzymatically converted into 6-methylmercaptopurine (6-MMP) by thiopurine-S-methyltransferase (TPMT) and into 6-thiouracic acid (6-TUA) by xanthine oxidase (XO). The remaining portion of mercaptopurine is converted into the biochemically active end-metabolites 6-thioguaninenucleotides (6-TGN, consisting of 6-thioguanine monophosphate, 6-thioguanine diphosphate and 6-thioguanine triphosphate) by a pathway of hypoxanthine-guanine phosphoribosyl transferase (HGPRT), inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate synthetase (GMPS). Thioguanine is metabolized by TPMT into 6-methylthioguanine (6-MTG) and into 6-TUA by guanine deaminase (GD) and XO. The remaining portion of thioguanine is directly converted into 6-TGN by HGPRT. Squared abbreviations display enzymatic conversions. Adapted from van Asseldonk et al[5].
See this image and copyright information in PMC

References

    1. Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, D’Haens G, D’Hoore A, Mantzaris G, Novacek G, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6:991–1030. - PubMed
    1. Dignass A, Van Assche G, Lindsay JO, Lémann M, Söderholm J, Colombel JF, Danese S, D’Hoore A, Gassull M, Gomollón F, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Current management. J Crohns Colitis. 2010;4:28–62. - PubMed
    1. Chande N, Patton PH, Tsoulis DJ, Thomas BS, MacDonald JK. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2015;10:CD000067. - PMC - PubMed
    1. Chande N, Tsoulis DJ, MacDonald JK. Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2013;4:CD000545. - PubMed
    1. Van Asseldonk DP, de Boer NK, Peters GJ, Veldkamp AI, Mulder CJ, Van Bodegraven AA. On therapeutic drug monitoring of thiopurines in inflammatory bowel disease; pharmacology, pharmacogenomics, drug intolerance and clinical relevance. Curr Drug Metab. 2009;10:981–997. - PubMed

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