title: Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease.
abstract: BACKGROUND
  The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by aminosalicylates has been described in an in vitro study. This could result in a higher risk of bone marrow depression when using the two drugs together.
  
  
  OBJECTIVE
  To investigate the in vivo interaction between azathioprine and aminosalicylates in quiescent Crohn's disease by measuring 6-thioguanine nucleotide levels, thiopurine methyltransferase activity and the plasma levels of the acetylated metabolite of 5-aminosalicylic acid.
  
  
  METHODS
  Sixteen patients taking a stable dose of azathioprine, plus sulfasalazine or mesalazine, were enrolled and completed the study. They were not taking any drugs interfering with azathioprine metabolism. Four visits every 4 weeks were held over a 3-month period. Aminosalicylate administration was withdrawn after the second visit. At each visit, the blood cell count, inflammatory parameters, levels of 6-thioguanine nucleotide and the acetylated metabolite of 5-aminosalicylic acid and thiopurine methyltransferase activity were determined.
  
  
  RESULTS
  After aminosalicylate withdrawal, mean 6-thioguanine nucleotide levels decreased significantly from 148 pmol (57-357 pmol) to 132 pmol (56-247 pmol) per 8 x 10(8) red blood cells (P=0.027), without significant changes in thiopurine methyltransferase activity or biological parameters.
  
  
  CONCLUSIONS
  This in vivo study favours the existence of an interaction between azathioprine and aminosalicylates through a mechanism which remains unclear. This drug-drug interaction should be taken into account when using azathioprine and aminosalicylates simultaneously.
authors.affiliation: Department of Gastroenterology, Catholic University of Louvain, Brussels, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Dewit
authors.forename: R
authors.initials: R
authors.lastname: Vanheuverzwyn
authors.forename: J P
authors.initials: JP
authors.lastname: Desager
authors.forename: Y
authors.initials: Y
authors.lastname: Horsmans
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology*; D001379:Azathioprine / Q000009:adverse effects* / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D003424:Crohn Disease / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology*; D008297:Male; D019804:Mesalamine / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology*; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D012460:Sulfasalazine / Q000009:adverse effects* / Q000494:pharmacology*; D013873:Thionucleotides / Q000097:blood*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D012460:Sulfasalazine; D019804:Mesalamine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine