Document Detail


A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine.
MedLine Citation:
PMID:  21122558     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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/8×10⁸ RBCs and 6-MMP>5000 pmol/8×10⁸ 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 100mg daily (range: 37.5-150 mg) to 25mg 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/8×10⁸ RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (± 4716) to 404.8 (± 332) pmol/8×10⁸ 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.
Authors:
Mark E Gerich; J Antonio Quiros; James P Marcin; Linda Tennyson; Maria Henthorn; Thomas P Prindiville
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Publication Detail:
Type:  Journal Article     Date:  2010-05-26
Journal Detail:
Title:  Journal of Crohn's & colitis     Volume:  4     ISSN:  1876-4479     ISO Abbreviation:  J Crohns Colitis     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-12-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101318676     Medline TA:  J Crohns Colitis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  546-52     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
Affiliation:
Department of Internal Medicine, Division of Gastroenterology, University of California Davis Health System, Sacramento, CA 95817, United States.
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