Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease.

Abstract

BACKGROUND:

Based on in vitro experiments using recombinant human thiopurine S-methyltransferase this enzyme is inhibited by sulfasalazine (sulphasalazine) and 5-aminosalicylate. Thus, during treatment with azathioprine or mercaptopurine, both metabolized by thiopurine S-methyltransferase, sulfasalazine or 5-aminosalicylate could modify the action of azathioprine/mercaptopurine.

AIMS:

To examine whether this interaction is effective under ex vivo conditions.

METHODS:

In 18 azathioprine-free patients and in 12 patients on azathioprine the inhibitory potential of sulfasalazine, 5-aminosalicylate and its metabolite (Ac-5-aminosalicylate) was assessed by ex vivo measurement of thiopurine S-methyltransferase in red blood cells.

RESULTS:

According to concentration response curves mean IC50 values (microm) for sulfasalazine, 5-aminosalicylate and Ac-5-aminosalicylate have been calculated in three groups of azathioprine-free patients and variable basal levels of thiopurine S-methyltransferase activity (very high, normal and intermediate). In all three groups sulfasalazine was the strongest inhibitor (IC50: 9-17 microm) if compared with 5-aminosalicylate (129-236) and Ac-5-aminosalicylate (58-74). In patients on azathioprine similar IC50 values have been calculated.

CONCLUSIONS:

Comparing human plasma concentrations of sulfasalazine (15-77 microm), 5-aminosalicylate (3-14 microm) and Ac-5-aminosalicylate (8-18 microm) with the IC50 values one can assume that only sulfasalazine would have the potential to inhibit thiopurine S-methyltransferase in vivo. However, the therapeutic impact should be proved by clinical studies.

• Authors: H Xin, C Fischer, M Schwab, U Klotz
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 21 Issue 9 Pg. 1105-9 (May 01 2005) ISSN: 0269-2813 [Print] England
• PMID: 15854172 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminosalicylic Acids
• Methyltransferases
• thiopurine methyltransferase

Topics

• Adolescent
• Adult
• Aminosalicylic Acids (therapeutic use)
• Drug Interactions
• Female
• Humans
• Inflammatory Bowel Diseases (drug therapy)
• Inhibitory Concentration 50
• Male
• Methyltransferases (metabolism)
• Middle Aged