Importance of 6-Thioguanine Nucleotide Metabolite Monitoring in Inflammatory Bowel Disease Patients Treated with Azathioprine

Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2019 May 1;40(1):73-79. doi: 10.2478/prilozi-2019-0006.

Abstract

The active metabolite of azathioprine, 6-thioguanine nucleotide (6-TGN) is the main component responsible for the immunosuppressive effect in treatment of inflammatory bowel disease (IBD). The aim of this study was to assess the correlation between the concentration of 6-thioguanine nucleotide and disease activity, azathioprine-related adverse effects and time duration of treatment in patients with inflammatory bowel disease. Thirty-four patients were included in this study. Type of disease, gender, time duration of therapy and adverse effects were recorded. Metabolite concentration was determined by high performance liquid chromatography. Twenty-one percent of patients have experienced an adverse effect, with leucocytopenia most commonly occurring (42.9%). More adverse effects were registered when patients were treated with azathioprine in a period of less than 3 months in comparison to the group of patients that have been under therapy between 3-12 months and more than 12 months (p˂0.05). Most of the patients that presented any adverse effect had high 6-TGN concentration (>450 pmol/8x108 Er). The mean value of 6-TGN metabolite concentration in IBD patients treated with azathioprine was 437.46 pmol/8x108 Er ± 198.82 pmol/8x108. The time duration of azathioprine treatment did not have any significant impact on the achieved 6-TGN concentration (p>0.05).Twenty patients (58.9%) had achieved remission after therapy initiation with azathioprine. More alertness is recommended to clinicians towards patients in the first 3 months of the therapy. Our study demonstrated that higher 6-TGN concentration is associated with azathioprine toxicity.

Keywords: 6-Thioguanine nucleotide; Inflammatory bowel disease; azathioprine.

MeSH terms

  • Adult
  • Azathioprine / adverse effects*
  • Azathioprine / therapeutic use
  • Drug Monitoring / methods
  • Female
  • Guanine Nucleotides / blood
  • Guanine Nucleotides / metabolism*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Thionucleotides / blood
  • Thionucleotides / metabolism*
  • Time Factors

Substances

  • Guanine Nucleotides
  • Immunosuppressive Agents
  • Thionucleotides
  • 6-thioguanylic acid
  • Azathioprine