Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease

Aliment Pharmacol Ther. 2009 Oct 15;30(8):843-53. doi: 10.1111/j.1365-2036.2009.04106.x. Epub 2009 Jul 24.

Abstract

Background: Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5-aminosalicylic acid, 5-ASA) were described.

Aim: To explore potential interactions between thiopurines and concomitant medications.

Methods: A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S-methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments.

Results: Based on TPMT genetics, 95% IBD patients were wild-type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7-29.5). No difference in TPMT activity was noted according to 5-ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose-effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co-treated with 5-ASA. In patients on active thiopurines also, 6-TGN and 6-MMP levels were evaluated and no significant difference was observed based on co-medication. TPMT activity was independently associated only with thiopurines dose (P = 0.016).

Conclusions: Our data suggest the absence of significant interactions between thiopurines and 5-ASA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Azathioprine / adverse effects*
  • DNA / genetics
  • Drug Interactions / genetics
  • Female
  • Genotype
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / genetics
  • Male
  • Mercaptopurine / adverse effects*
  • Mesalamine / adverse effects*
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Prospective Studies
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunosuppressive Agents
  • Mesalamine
  • DNA
  • Mercaptopurine
  • Azathioprine