Enhanced bioavailability of azathioprine compared to 6-mercaptopurine therapy in inflammatory bowel disease: correlation with treatment efficacy

Aliment Pharmacol Ther. 2000 Aug;14(8):1009-14. doi: 10.1046/j.1365-2036.2000.00812.x.


Background: Azathioprine and 6-mercaptopurine have proven efficacy in the treatment of Crohn's disease. Immunosuppression is mediated by their intracellular metabolism into active 6-thioguanine metabolites, and clinical responsiveness to therapy in patients with inflammatory bowel disease has been correlated with the measure of erythrocyte 6-thioguanine levels.

Aims and methods: To perform a dosing equivalency analysis and comparison of clinical efficacy in 82 patients with inflammatory bowel disease on long-term (> 2 months) therapy with either branded azathioprine (Imuran) (n=26), generic azathioprine (n=38), or 6-mercaptopurine (n=18), based on the measurement of erythrocyte 6-thioguanine metabolite levels.

Results: Disease remission was achieved in 51% (42 out of 82) of patients treated with either azathioprine or 6-mercaptopurine therapy, and correlated well with high erythrocyte 6-thioguanine levels (> 250 pmoles/8 x 108 RBCs). Patients treated with either branded azathioprine or 6-mercaptopurine achieved significantly higher erythrocyte 6-thioguanine levels than patients treated with generic azathioprine, thereby suggesting that branded azathioprine has improved oral bioavailability compared to generic azathioprine. These data are consistent with the putative immunosuppressive role of 6-thioguanine metabolites in the treatment of inflammatory bowel disease, and provides a basis for developing a therapeutic index of clinical efficacy based on the measurement of erythrocyte 6-thioguanine metabolite levels.

Conclusions: Our results suggest that differences in bioavailability may have clinical relevance when considering the need to optimize erythrocyte 6-thioguanine metabolite levels in patients deemed unresponsive to treatment on conventional drug dosages.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Azathioprine / pharmacokinetics*
  • Azathioprine / therapeutic use
  • Biological Availability
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Mercaptopurine / pharmacokinetics*
  • Mercaptopurine / therapeutic use
  • Therapeutic Equivalency
  • Treatment Outcome


  • Immunosuppressive Agents
  • Mercaptopurine
  • Azathioprine