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Azathioprine and 6-mercaptopurine in inflammatory bowel disease

Authors
Yousif I A-Rahim, MD, PhD
Richard J Farrell, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH

INTRODUCTION

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 the treatment of inflammatory bowel disease with 6-MP or azathioprine" 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".)

PHARMACODYNAMICS

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: Nov 2016. | This topic last updated: Mon Dec 21 00:00:00 GMT+00:00 2015.
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