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

Aliment Pharmacol Ther. 2005 Sep 1;22(5):441-6. doi: 10.1111/j.1365-2036.2005.02583.x.


Background: Many non-responders to azathioprine or mercaptopurine (6-mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6-methylmercaptopurine 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 x 10(8) red blood cells (P < 0.001), while 6-methylmercaptopurine decreased from a mean of 10 380 +/- 1245 to 1732 +/- 502 pmol/8 x 10(8) 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 x 10(8)/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.

Publication types

  • Multicenter Study

MeSH terms

  • Allopurinol / therapeutic use*
  • Antimetabolites / therapeutic use*
  • Azathioprine / therapeutic use*
  • Drug Combinations
  • Drug Resistance
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammatory Bowel Diseases / drug therapy*
  • Mercaptopurine / therapeutic use*
  • Thioguanine / metabolism


  • Antimetabolites
  • Drug Combinations
  • Immunosuppressive Agents
  • Allopurinol
  • Mercaptopurine
  • Thioguanine
  • Azathioprine