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.

AIM:

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 Aminosalicylate administration was withdrawn after the second visit.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: O Dewit, R Vanheuverzwyn, J P Desager, Y Horsmans
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 16 Issue 1 Pg. 79-85 (Jan 2002) ISSN: 0269-2813 [Print] England
• PMID: 11856081 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Biomarkers
• Guanine Nucleotides
• Immunosuppressive Agents
• Thionucleotides
• 6-thioguanylic acid
• Sulfasalazine
• Mesalamine
• Methyltransferases
• thiopurine methyltransferase
• Azathioprine

Topics

• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, pharmacology)
• Azathioprine (adverse effects, pharmacology)
• Biomarkers (analysis)
• Crohn Disease (drug therapy)
• Drug Interactions
• Female
• Guanine Nucleotides (blood)
• Humans
• Immunosuppressive Agents (adverse effects, pharmacology)
• Male
• Mesalamine (adverse effects, metabolism, pharmacology)
• Methyltransferases (metabolism)
• Middle Aged
• Sulfasalazine (adverse effects, pharmacology)
• Thionucleotides (blood)