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

Abstract

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
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 4 Issue 5 Pg. 546-52 (Nov 2010) ISSN: 1876-4479 [Electronic] England
• PMID: 21122558 (Publication Type: Journal Article)
• Copyright: Published by Elsevier B.V.

Chemical References

• Enzyme Inhibitors
• Guanine Nucleotides
• Immunosuppressive Agents
• Thionucleotides
• 6-thioguanylic acid
• Allopurinol
• 6-methylthiopurine
• Mercaptopurine
• Methyltransferases
• thiopurine methyltransferase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Allopurinol (administration & dosage, pharmacology, therapeutic use)
• Child
• Child, Preschool
• Drug Administration Schedule
• Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Female
• Guanine Nucleotides (blood)
• Humans
• Immunosuppressive Agents (administration & dosage, metabolism, therapeutic use)
• Inflammatory Bowel Diseases (drug therapy, enzymology, metabolism)
• Male
• Mercaptopurine (administration & dosage, analogs & derivatives, blood, metabolism, therapeutic use)
• Methyltransferases (genetics, metabolism)
• Middle Aged
• Phenotype
• Prevalence
• Prospective Studies
• Thionucleotides (blood)
• Young Adult