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Azathioprine and 6-mercaptopurine in inflammatory bowel disease

Yousif I A-Rahim, MD, PhD
Richard J Farrell, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Immunomodulatory drugs, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), exert a steroid-sparing effect in patients with steroid-dependent and steroid-refractory inflammatory bowel disease. While azathioprine (AZA) and 6-mercaptopurine (6-MP) have been noted to induce and maintain remission in ulcerative colitis and Crohn disease, their use is limited by concerns of toxicity.

This topic review summarizes the pharmacology, dosing, monitoring, and adverse effects of AZA and 6-MP in inflammatory bowel disease. 6-MP metabolite monitoring and thiopurine-S-methyltransferase (TPMT) testing in the treatment of inflammatory bowel disease, indications and efficacy of AZA and 6-MP in ulcerative colitis and Crohn disease are presented separately. (See "6-mercaptopurine (6-MP) metabolite monitoring and TPMT testing in patients with inflammatory bowel disease" and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis" and "Immunomodulator therapy in Crohn disease" and "Overview of the medical management of severe or refractory Crohn disease in adults".)


Azathioprine (AZA) is a prodrug that is quickly converted to 6-mercaptopurine (6-MP) via a nonenzymatic nucleophilic attack by sulfhydryl-containing compounds, such as glutathione, present in red blood cells and other tissues. 6-MP is then metabolized in the liver and gut by one of three enzymes (figure 1) [1,2]:

Thiopurine-S-methyltransferase (TPMT), which catalyzes the methylation of 6-MP to an inactive metabolite 6-methyl-mercaptopurine (6-MMP)

Xanthine oxidase, which catalyzes 6-MP to inactive thiourate

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Literature review current through: Oct 2017. | This topic last updated: Dec 21, 2015.
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