Background: 6-mercaptopurine (6-MP) is used for the induction and maintenance of remission of inflammatory bowel disease (IBD). 6-MP is converted into 6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. This study prospectively evaluated the effect of allopurinol on 6-MP metabolites in adult and pediatric IBD patients. Additionally, we quantified the prevalence of preferential metabolism towards 6-MMP through a retrospective analysis of IBD patients. Methods: Twenty patients (10 adult; 10 pediatric) with evidence of preferential metabolism towards 6-MMP, (6-TGN<250pmol/8X108RBCs and 6-MMP>5000pmol/8X108RBCs) were prospectively treated with allopurinol 100mg daily and up to 100mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement. Results: The median dose of 6-MP for adults decreased from 100mg daily (range: 37.5-150mg) to 25mg daily (range: 12.5-50mg). The median dose of 6-MP for pediatric patients decreased from 50mg (range: 25-50mg) to 10.7mg (range: 10.7 to 21.4mg). Mean 6-TGN levels in all subjects increased from 197.4 (±59) to 284.8 (±107) pmol/8X108RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (±4716) to 404.8 (±332) pmol/8x108RBCs (p=0.0004). There were no complications associated with allopurinol therapy. Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism towards 6-MMP. The proportion of preferential metabolism was equal in adults and pediatric patients. Conclusion: Our results indicate that the addition of allopurinol safely shifts metabolite production in both adult and pediatric IBD patients and that there is a high prevalence of preferential metabolism towards 6-MMP among IBD patients.
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