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Allopurinol might improve response to azathioprine and 6‐mercaptopurine by correcting an unfavorable metabolite ratio
Author(s) -
Gardiner Sharon J,
Gearry Richard B,
Burt Michael J,
ChalmersWatson Teresa,
Chapman Bruce A,
Ross Alison G,
Stedman Catherine A M,
Huelsen Alexander,
Barclay Murray L
Publication year - 2011
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2010.06489.x
Subject(s) - allopurinol , azathioprine , thiopurine methyltransferase , medicine , metabolite , mercaptopurine , pharmacology , gastroenterology , disease
Background and Aim: Allopurinol potentiates azathioprine and 6‐mercaptopurine (6‐MP) by increasing 6‐thioguanine nucleotide (6‐TGN) metabolite concentrations. The outcome might also be improved by adding allopurinol in individuals who preferentially produce 6‐methylmercaptopurine nucleotides (6‐MMPN), rather than 6‐TGN. The aim of the present study was to investigate the effect of allopurinol on concentrations of 6‐MMPN and 6‐TGN in individuals with a high ratio of these metabolites (>20), which is indicative of a poor thiopurine response. Methods: Sixteen individuals were identified who were taking azathioprine or 6‐MP, and were commenced on allopurinol to improve a high 6‐MMPN : TGN ratio. Metabolite concentrations were compared before and after commencing allopurinol, and markers of disease control were compared. Results: The addition of 100–300 mg allopurinol daily and thiopurine dose reduction (17–50% of the original dose) resulted in a reduction of the median (and range) 6‐MMPN concentration, from 11 643 (3 365–27 832) to 221 (55–844) pmol/8 × 10 8 red blood cells (RBC; P = 0.0005), increased 6‐TGN from 162 (125–300) to 332 (135–923) pmol/8 × 10 8 RBC ( P = 0.0005), and reduced the 6‐MMPN : 6‐TGN ratio from 63 (12–199) to 1 (0.1–4.5) ( P = 0.0005). There was a significant reduction in steroid dose requirements at 12 months ( P = 0.04) and trends for improvement in other markers of disease control. One patient developed red cell aplasia that resolved upon stopping azathioprine and allopurinol. Conclusions: In those with a high 6‐MMPN : 6‐TGN ratio (>20), response to thiopurine treatment might be improved by the addition of allopurinol, together with a reduced thiopurine dose and close hematological monitoring.