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

M. P. Sparrow, S. A. Hande, S. Friedman, W. C. Lim, S. I. Reddy, D. Cao, S. B. Hanauer

Research output: Contribution to journalArticleResearchpeer-review

154 Citations (Scopus)

Abstract

Background: Many non-responders to azathioprine or mercaptopurine (6-mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6-methyl-mercaptopurine instead of the active 6-tioguanine (6-tioguanine) metabolites. Aim: To describe the use of allopurinol in mercaptopurine/azathioprine non-responders to deliberately shunt metabolism of mercaptopurine towards 6-tioguanine. Methods: Fifteen thiopurine non-responders whose metabolites demonstrated preferential metabolism towards 6-methylmercaptopurine are described. Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to 25-50% of the original dose. Patients were followed clinically and with serial 6-tioguanine and 6-methylmercaptopurine metabolite measurements. Results: After initiating allopurinol, 6-tioguanine levels increased from a mean of 185.73 ± 17.7 to 385.4 ± 41.5 pmol/8 × 108 red blood cells (P < 0.001), while 6-methylmercaptopurine decreased from a mean of 10 380 ± 1245 to 1732 ± 502 pmol/8 × 108 RBCs (P < 0.001). Allopurinol led to a decrease in white blood cell from a mean of 8.28 ± 0.95 to 6.1 ± 0.82 × 108/L (P = 0.01). Conclusions: The addition of allopurinol to thiopurine non-responders with preferential shunting to 6-methylmercaptopurine metabolites appears to be an effective means to shift metabolism towards 6-tioguanine.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
JournalAlimentary Pharmacology and Therapeutics
Volume22
Issue number5
DOIs
Publication statusPublished - 1 Sep 2005
Externally publishedYes

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