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

Journal Title: Alimentary pharmacology & therapeutics 2005-05, Vol.21 (9), p.1105-1109
Main Author: Xin, H
Other Authors: Fischer, C , Schwab, M , Klotz, U
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Oxford, UK: Blackwell Publishing
ID: ISSN: 0953-0673
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recordid: cdi_crossref_primary_10_1111_j_1365_2036_2005_02460_x
title: Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease
format: Article
creator:
  • Xin, H
  • Fischer, C
  • Schwab, M
  • Klotz, U
subjects:
  • Adolescent
  • Adult
  • Aminosalicylic Acids - therapeutic use
  • Biological and medical sciences
  • Digestive system
  • Drug Interactions
  • Female
  • Gastroenterology. Liver. Pancreas. Abdomen
  • Humans
  • Inflammatory Bowel Diseases - drug therapy
  • Inhibitory Concentration 50
  • Male
  • Medical sciences
  • Methyltransferases - metabolism
  • Middle Aged
  • Pharmacology. Drug treatments
ispartof: Alimentary pharmacology & therapeutics, 2005-05, Vol.21 (9), p.1105-1109
description: 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 IC50 values (μm) 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 μm) 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 μm), 5-aminosalicylate (3–14 μm) and Ac-5-aminosalicylate (8–18 μm) 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.
language: eng
source:
identifier: ISSN: 0953-0673
fulltext: no_fulltext
issn:
  • 0953-0673
  • 0269-2813
  • 1365-2036
url: Link


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titleEffects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease
creatorXin, H ; Fischer, C ; Schwab, M ; Klotz, U
creatorcontribXin, H ; Fischer, C ; Schwab, M ; Klotz, U
descriptionSummary 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 (μm) 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 μm) 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 μm), 5-aminosalicylate (3–14 μm) and Ac-5-aminosalicylate (8–18 μm) 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.
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subjectAdolescent ; Adult ; Aminosalicylic Acids - therapeutic use ; Biological and medical sciences ; Digestive system ; Drug Interactions ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Inflammatory Bowel Diseases - drug therapy ; Inhibitory Concentration 50 ; Male ; Medical sciences ; Methyltransferases - metabolism ; Middle Aged ; Pharmacology. Drug treatments
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descriptionSummary 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 (μm) 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 μm) 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 μm), 5-aminosalicylate (3–14 μm) and Ac-5-aminosalicylate (8–18 μm) 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.
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atitleEffects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease
jtitleAlimentary pharmacology & therapeutics
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date2005-05
risdate2005
volume21
issue9
spage1105
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pages1105-1109
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00953-0673
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notesPresent address: Department of Clinical Pharmacology, Wuhan General Hospital, Wuhan, China.
abstractSummary 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 (μm) 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 μm) 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 μm), 5-aminosalicylate (3–14 μm) and Ac-5-aminosalicylate (8–18 μm) 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.
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