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Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43.

Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety.

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1
Pediatric IBD Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Abstract

6-Mercaptopurine and its prodrug azathioprine remain the mainstay of immunomodulator therapy for the maintenance of a steroid-free remission in patients with IBD. Recent evidence suggests that the cytotoxic and immunosuppressive effects of azathioprine might be mediated via the induction of lymphocyte apoptosis by its active metabolites, 6-thioguanine nucleotides. The therapeutic benefits of thiopurines have been shown to correlate with the concentration of 6-thioguanine nucleotides. Inherited differences in drug metabolism and disposition can significantly impact the safety and efficacy of these drugs. The thiopurine methyltransferase enzyme plays an important role in the metabolism of 6-mercaptopurine and azathioprine and in the determination of thiopurine cytotoxicity. By gaining an understanding of the pharmacology and metabolism of thiopurine therapy and putting it into the clinical context, clinicians will be able to optimize thiopurine therapy in IBD.

PMID:
15354273
[Indexed for MEDLINE]
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