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.
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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)
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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
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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
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