Skip to main content
Log in

Interruption of Mesalamine and Reduction of the Blood Concentration of the Active Metabolites of Azathioprine: Possible Causes of Ulcerative Colitis Relapse

  • CASE REPORT
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Stocco G, Martelossi S, Barabino A, Decorti G, Bartoli F, Montico M, Gotti A, Ventura A (2007) Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease. Inflamm Bowel Dis 13:57–64. doi:10.1002/ibd.20004

    Article  PubMed  Google Scholar 

  2. Marinaki AM, Duley JA, Arenas M, Ansari A, Sumi S, Lewis CM, Shobowale-Bakre M, Fairbanks LD, Sanderson J (2004) Mutation in the itpa gene predicts intolerance to azathioprine. Nucleosides Nucleotides Nucleic Acids 23:1393–1397. doi:10.1081/NCN-200027639

    Article  PubMed  CAS  Google Scholar 

  3. Dervieux T, Boulieu R (1998) Simultaneous determination of 6-thioguanine and methyl 6-mercaptopurine nucleotides of azathioprine in red blood cells by HPLC. Clin Chem 44:551–555

    PubMed  CAS  Google Scholar 

  4. Timmer A, McDonald J, Macdonald J (2007) Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev CD000478

  5. Barabino A, Torrente F, Ventura A, Cucchiara S, Castro M, Barbera C (2002) Azathioprine in paediatric inflammatory bowel disease: an italian multicentre survey. Aliment Pharmacol Ther 16:1125–1130. doi:10.1046/j.1365-2036.2002.01269.x

    Article  PubMed  CAS  Google Scholar 

  6. Elion GB (1989) The purine path to chemotherapy. Science 244:41–47. doi:10.1126/science.2649979

    Article  PubMed  CAS  Google Scholar 

  7. Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, Soule JC, Modigliani R, Touze Y, Catala P, Libersa C, Broly F (2000) Genotypic analysis of thiopurine S-methyltransferase in patients with crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 118:1025–1030. doi:10.1016/S0016-5085(00)70354-4

    Article  PubMed  CAS  Google Scholar 

  8. Bokemeyer B, Teml A, Roggel C, Hartmann P, Fischer C, Schaeffeler E, Schwab M (2007) Adherence to thiopurine treatment in out-patients with Crohn's disease. Aliment Pharmacol Ther 26:217–225

    Article  PubMed  CAS  Google Scholar 

  9. Palmieri O, Latiano A, Bossa F, Vecchi M, D'Inca R, Guagnozzi D, Tonelli F, Cucchiara S, Valvano MR, Latiano T, Andriulli A, Annese V (2007) Sequential evaluation of thiopurine methyltransferase, inosine triphosphate pyrophosphatase, and hprt1 genes polymorphisms to explain thiopurines’ toxicity and efficacy. Aliment Pharmacol Ther 26:737–745

    Article  PubMed  CAS  Google Scholar 

  10. Teml A, Schaeffeler E, Herrlinger KR, Klotz U, Schwab M (2007) Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing. Clin Pharmacokinet 46:187–208. doi:10.2165/00003088-200746030-00001

    Article  PubMed  CAS  Google Scholar 

  11. Lowry PW, Franklin CL, Weaver AL, Szumlanski CL, Mays DC, Loftus EV, Tremaine WJ, Lipsky JJ, Weinshilboum RM, Sandborn WJ (2001) Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut 49:656–664. doi:10.1136/gut.49.5.656

    Article  PubMed  CAS  Google Scholar 

  12. Hande S, Wilson-Rich N, Bousvaros A, Zholudev A, Maurer R, Banks P, Makrauer F, Reddy S, Burakoff R, Friedman S (2006) 5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine. Inflamm Bowel Dis 12:251–257. doi:10.1097/01.MIB.0000206544.05661.9f

    Article  PubMed  Google Scholar 

  13. de Boer NK, Wong DR, Jharap B, de Graaf P, Hooymans PM, Mulder CJ, Rijmen F, Engels LG, van Bodegraven AA (2007) Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism. Am J Gastroenterol 102:2747–2753. doi:10.1111/j.1572-0241.2007.01511.x

    Article  PubMed  CAS  Google Scholar 

  14. Xin H, Fischer C, Schwab M, Klotz U (2005) Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease. Aliment Pharmacol Ther 21:1105–1109. doi:10.1111/j.1365-2036.2005.02460.x

    Article  PubMed  CAS  Google Scholar 

  15. Lewis LD, Benin A, Szumlanski CL, Otterness DM, Lennard L, Weinshilboum RM, Nierenberg DW (1997) Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug–drug interaction. Clin Pharmacol Ther 62:464–475. doi:10.1016/S0009-9236(97)90125-9

    Article  PubMed  CAS  Google Scholar 

  16. Present DH (2000) Interaction of 6-mercaptopurine and azathioprine with 5-aminosalicylic acid agents. Gastroenterology 119:276

    PubMed  CAS  Google Scholar 

  17. Stocco G, Martelossi S, Barabino A, Fontana M, Lionetti P, Decorti G, Malusa N, Bartoli F, Fezzi M, Giraldi T, Ventura A (2005) Tpmt genotype and the use of thiopurines in paediatric inflammatory bowel disease. Dig Liver Dis 37:940–945. doi:10.1016/j.dld.2005.08.003

    Article  PubMed  CAS  Google Scholar 

  18. Dilger K, Schaeffeler E, Lukas M, Strauch U, Herfarth H, Muller R, Schwab M (2007) Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn's disease during 1 year of treatment with azathioprine or mesalazine. Ther Drug Monit 29:1–5. doi:10.1097/FTD.0b013e3180312b9a

    Article  PubMed  CAS  Google Scholar 

  19. Ricart E, Taylor WR, Loftus EV, O'Kane D, Weinshilboum RM, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ (2002) N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis. Am J Gastroenterol 97:1763–1768. doi:10.1111/j.1572-0241.2002.05838.x

    Article  PubMed  CAS  Google Scholar 

  20. Chen M, Xia B, Chen B, Guo Q, Li J, Ye M, Hu Z (2007) N-acetyltransferase 2 slow acetylator genotype associated with adverse effects of sulphasalazine in the treatment of inflammatory bowel disease. Can J Gastroenterol 21:155–158

    PubMed  Google Scholar 

Download references

Acknowledgments

The research was supported by grants from the Italian Ministry of University and Scientific Research (PRIN projects 2004065777 and 2005065797) and the Italian Ministry of Health. Dr. Gabriele Stocco and Dr. Sara Marino are recipients of a research fellowships from IRCCS “Burlo Garofolo,” Trieste.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriele Stocco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stocco, G., Martelossi, S., Malusa’, N. et al. Interruption of Mesalamine and Reduction of the Blood Concentration of the Active Metabolites of Azathioprine: Possible Causes of Ulcerative Colitis Relapse. Dig Dis Sci 53, 3246–3249 (2008). https://doi.org/10.1007/s10620-008-0283-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0283-1

Keywords

Navigation