Review
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World J Gastroenterol. Oct 7, 2011; 17(37): 4166-4173
Published online Oct 7, 2011. doi: 10.3748/wjg.v17.i37.4166
Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease
Kara Bradford, David Q Shih
Kara Bradford, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
David Q Shih, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Author contributions: Bradford K and Shih DQ solely contributed to this paper.
Supported by Grant from Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center
Correspondence to: David Q Shih, MD, PhD, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 4066, Los Angeles, CA 90048, United States. david.shih@csmc.edu
Telephone: +1-310-4237722 Fax: +1-310-4230224
Received: March 22, 2011
Revised: June 20, 2011
Accepted: June 27, 2011
Published online: October 7, 2011
Abstract

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP.

Keywords: Azathioprine; Drug levels; Inflammatory bowel disease; 6-Mercaptopurine; Thiopurine