Literature DB >> 18299738

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: a review of four cases and the literature.

T N Witte1, A L Ginsberg.   

Abstract

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment.
RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8 x 10(8) red blood cells. Two patients experienced reversible leukopenia.
CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised.

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Year:  2008        PMID: 18299738      PMCID: PMC2659140          DOI: 10.1155/2008/870981

Source DB:  PubMed          Journal:  Can J Gastroenterol        ISSN: 0835-7900            Impact factor:   3.522


  31 in total

1.  Effect of allopurinol on the intestinal absorption of 6-mercaptopurine in rats.

Authors:  H Sasaki; K Tsuru; J Nakamura; R Konishi; J Shibasaki
Journal:  J Pharmacobiodyn       Date:  1987-12

2.  Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis.

Authors:  P D R Higgins; M Schwartz; J Mapili; I Krokos; J Leung; E M Zimmermann
Journal:  Gut       Date:  2005-06       Impact factor: 23.059

3.  Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine.

Authors:  M P Sparrow; S A Hande; S Friedman; W C Lim; S I Reddy; D Cao; S B Hanauer
Journal:  Aliment Pharmacol Ther       Date:  2005-09-01       Impact factor: 8.171

4.  Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group.

Authors:  W J Sandborn; W J Tremaine; D C Wolf; S R Targan; C A Sninsky; L R Sutherland; S B Hanauer; J W McDonald; B G Feagan; R N Fedorak; K L Isaacs; M G Pike; D C Mays; J J Lipsky; S Gordon; C S Kleoudis; R H Murdock
Journal:  Gastroenterology       Date:  1999-09       Impact factor: 22.682

5.  Azathioprine induced nodular regenerative hyperplasia in IBD patients.

Authors:  Fady Daniel; Jean-François Cadranel; Philippe Seksik; Alain Cazier; Jean-Paul Duong Van Huyen; Marianne Ziol; Pierre Coutarel; Patrick Loison; Raymond Jian; Philippe Marteau
Journal:  Gastroenterol Clin Biol       Date:  2005-05

6.  Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

Authors:  P Chocair; J Duley; H A Simmonds; J S Cameron; L Ianhez; S Arap; E Sabbaga
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7.  Kinetics of mercaptopurine and thioguanine nucleotides in renal transplant recipients during azathioprine treatment.

Authors:  S Bergan; H E Rugstad; O Bentdal; L Endresen; O Stokke
Journal:  Ther Drug Monit       Date:  1994-02       Impact factor: 3.681

8.  A simple clinical colitis activity index.

Authors:  R S Walmsley; R C Ayres; R E Pounder; R N Allan
Journal:  Gut       Date:  1998-07       Impact factor: 23.059

9.  Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol.

Authors:  S Zimm; J M Collins; D O'Neill; B A Chabner; D G Poplack
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10.  The inhibitory effects of allopurinol on the production and cytotoxicity of tumor necrosis factor.

Authors:  T Oláh; K Régely; Y Mándi
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  1994-07       Impact factor: 3.000

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  5 in total

Review 1.  Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease.

Authors:  Kara Bradford; David Q Shih
Journal:  World J Gastroenterol       Date:  2011-10-07       Impact factor: 5.742

Review 2.  Optimizing conventional therapies for inflammatory bowel disease.

Authors:  Miles P Sparrow; Peter M Irving; Stephen B Hanauer
Journal:  Curr Gastroenterol Rep       Date:  2009-12

3.  Combination of thiopurines and allopurinol: adverse events and clinical benefit in IBD.

Authors:  Shail M Govani; Peter D R Higgins
Journal:  J Crohns Colitis       Date:  2010-03-21       Impact factor: 9.071

Review 4.  Inflammatory bowel disease in the elderly.

Authors:  Syed Wasif Hussain; Darrell S Pardi
Journal:  Drugs Aging       Date:  2010-08-01       Impact factor: 3.923

5.  Low allopurinol doses are sufficient to optimize azathioprine therapy in inflammatory bowel disease patients with inadequate thiopurine metabolite concentrations.

Authors:  Ivanka Curkovic; Katharina M Rentsch; Pascal Frei; Michael Fried; Gerhard Rogler; Gerd A Kullak-Ublick; Alexander Jetter
Journal:  Eur J Clin Pharmacol       Date:  2013-04-16       Impact factor: 2.953

  5 in total

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