6-Thioguanine Seems Promising in Azathioprine- Or 6-mercaptopurine-intolerant Inflammatory Bowel Disease Patients: A Short-Term Safety Assessment

Eur J Gastroenterol Hepatol. 2003 Jan;15(1):63-7. doi: 10.1097/00042737-200301000-00011.


Objective: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have proven efficacy in the treatment of inflammatory bowel disease (IBD). However, adverse events leading to discontinuation may occur in 10-20% of patients. The efficacy of AZA and 6-MP is based on formation of their active metabolites, the 6-thioguaninenucleotides (6-TGNs). Therefore, 6-thioguanine (6-TG), an agent leading more directly to the formation of 6-TGNs and until recently used only in patients suffering from leukaemia, may be an alternative in AZA or 6-MP intolerance. The purpose of our study was to assess the short-term safety of 6-TG.

Methods: Thirty-two IBD patients with previously established AZA or 6-MP intolerance were treated with 6-TG in doses of 20 mg (n = 19) or 40 mg (n = 13) once daily. Safety parameters were obtained at 0, 1, 2, 4 and 8 weeks after start of medication. Primary outcome measures were the ability to tolerate 6-TG and the occurrence of adverse events. Secondary outcome definitions included laboratory parameters.

Results: Twenty-six (81%) patients were able to tolerate 6-TG during the first 8 weeks. In three of six patients, side effects leading to discontinuation were probably (n = 2) or obviously (n = 1) related to 6-TG. No clinically relevant haematological events or hepatotoxicity occurred in the observed period. Steady-state 6-TG levels were significantly higher with 40 mg once daily (1621 +/- 828 picomol/8 x 10(8) red blood cells (RBC)) than with 20 mg once daily (937 +/- 325 picomol/8 x 10(8) RBC; n = 0.001).

Conclusions: 6-TG treatment seems promising in AZA- or 6-MP-intolerant IBD patients. However, long-term safety and efficacy have yet to be determined.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Azathioprine / adverse effects
  • Chemical and Drug Induced Liver Injury
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Erythrocytes / metabolism
  • Female
  • Gastrointestinal Agents / adverse effects*
  • Gastrointestinal Agents / blood
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / blood
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Male
  • Mercaptopurine / adverse effects
  • Mercaptopurine / analogs & derivatives*
  • Mercaptopurine / blood
  • Middle Aged
  • Prospective Studies
  • Thioguanine / adverse effects*
  • Thioguanine / blood


  • Gastrointestinal Agents
  • Immunosuppressive Agents
  • 6-methylthiopurine
  • Mercaptopurine
  • Thioguanine
  • Azathioprine