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Anne M. Griffiths, Monitoring of Azathioprine/6-mercaptopurine Treatment in Children With IBD Is Not Necessary, Inflammatory Bowel Diseases, Volume 9, Issue 6, 1 November 2003, Pages 389–391, https://doi.org/10.1097/00054725-200311000-00008
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The efficacy of 6-mercaptopurine (6-MP) and its pro-drug, azathioprine (AZA), in Crohn's disease is clearly documented by meta-analyses of randomized controlled trial data (1). The importance of these steroid-sparing agents in controlling intestinal inflammation and thereby ameliorating growth in pediatric patients with Crohn's disease is now well established (2). Randomized controlled trials examining the role of AZA/6MP in ulcerative colitis are relatively few, but placebo-controlled double-blind withdrawal trial data have demonstrated a benefit in the maintenance of clinical remission (3). What is debated herein is not the efficacy of AZA/6MP in IBD, but the necessity for and utility of metabolizing enzyme assessment and routine metabolite monitoring among patients receiving such immunomodulatory therapy.
As depicted in Figure 1, AZA undergoes of series of enzymatic reactions leading to the formation of 6-thioguanine nucleotides (6-TGN), considered the active, but myelotoxic, metabolites. These nucleotides are incorporated into DNA with resultant cytotoxicity. In competing enzymatic pathways, thiopurine methyltransferase (TPMT) catalyzes the formation of 6-methyl-mercaptopurine ribonucleotides (6-MMPR), metabolites that are therapeutically inactive and potentially hepatotoxic.
