A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine

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 <250 pmol/8 x 10(8) RBCs and 6 MMP> 5000 pmol/8 x 10(8) RBCs) were prospectively treated with allopurinol 100 mg daily and up to 100 mg 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 100 mg daily (range 37 5-150 mg) to 25 mg daily (range 12 5-50 mg) The median dose of 6 MP for pediatric patients decreased from 50 mg (range 25-50 mg) to 10 7 mg (range 10 7 to 21 4 mg) Mean 6 TGN levels in all subjects increased from 197 4 (+/- 59) to 284 8 (+/- 107) pmol/8 x 10(8) RBCs (p = 0 0005) Mean 6 MMP levels in all subjects decreased from a mean of 7719 8 (+/- 4716) to 404 8 (+/- 332) pmol/8 x 10(8) RBCs (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 Published by Elsevier B V on behalf of European Crohn s and Colitis Organisation