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Effects of aminosalicylates on thiopurine S‐methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease
Author(s) -
Xin H.,
Fischer C.,
Schwab M.,
Klotz U.
Publication year - 2005
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2005.02460.x
Subject(s) - sulfasalazine , azathioprine , thiopurine methyltransferase , pharmacology , chemistry , ex vivo , in vivo , medicine , biochemistry , in vitro , ulcerative colitis , biology , microbiology and biotechnology , disease
Summary 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 IC 50 values ( μ m ) 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 (IC 50 : 9–17 μ m ) if compared with 5‐aminosalicylate (129–236) and Ac‐5‐aminosalicylate (58–74). In patients on azathioprine similar IC 50 values have been calculated. Conclusions : Comparing human plasma concentrations of sulfasalazine (15–77 μ m ), 5‐aminosalicylate (3–14 μ m ) and Ac‐5‐aminosalicylate (8–18 μ m ) with the IC 50 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.