Monitoring 6-thioguanine nucleotide concentrations in Japanese patients with inflammatory bowel disease

J Gastroenterol Hepatol. 2008 Sep;23(9):1373-7. doi: 10.1111/j.1440-1746.2008.05419.x. Epub 2008 Jul 23.

Abstract

Background and aim: There have been no reports on 6-thioguanine nucleotide (6-TGN) concentrations in Japanese patients with inflammatory bowel disease (IBD) undergoing azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy. The aim of this study was to assess 6-TGN concentrations in Japanese IBD patients.

Methods: Eighty-three patients with Crohn's disease (n = 42) and ulcerative colitis (n = 41) were enrolled. In 69 patients, AZA was prescribed at 50 mg/day, and seven patients were given 75 (n = 5) or 100 mg/day (n = 2). 6-MP was administered at 30 mg/day (n = 7). The 6-TGN concentrations were then assayed by high-performance liquid chromatography.

Results: The mean 6-TGN concentrations of the entire study population (n = 83) were 277.9 +/- 179.8 pmol/8 x 10(8) red blood cells (RBC). The mean 6-TGN concentrations in those patients with active disease (n = 38) and those in remission (n = 45) were 232.9 +/- 159.7(mean +/- SD) and 342.8 +/- 184.6 pmol/8 x 10(8) RBC, respectively (P < 0.05). The odds ratio of being in remission and having a 6-TGN value >235 pmol/8 x 10(8) RBC was 2.6 (95% CI 1.05-6.2). A significant inverse correlation was found between the white blood cell (WBC) counts and 6-TGN concentrations (r = -0.301, P < 0.05, n = 83); the mean WBC counts of the active patients (6780 +/- 2412) were significantly higher than the patients in clinical remission (5468 +/- 1920, P < 0.05). Three patients with severe leukopenia and 10 patients with high 6-TGN concentrations had no thiopurine S-methyl transferase mutations.

Conclusion: The 6-TGN concentrations in Japanese patients with IBD on low-dose AZA and 6-MP therapy were comparable to those reported from Western countries. The monitoring of 6-TGN concentrations may be helpful for developing a therapeutic strategy for Japanese IBD patients.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Azathioprine / administration & dosage
  • Azathioprine / blood
  • Azathioprine / therapeutic use*
  • Biomarkers, Pharmacological / blood
  • Chromatography, High Pressure Liquid
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Drug Monitoring / methods*
  • Erythrocyte Count
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use*
  • Japan
  • Leukocyte Count
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / blood
  • Mercaptopurine / therapeutic use*
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mutation
  • Odds Ratio
  • Remission Induction
  • Thioguanine / blood*
  • Treatment Outcome

Substances

  • Biomarkers, Pharmacological
  • Immunosuppressive Agents
  • Mercaptopurine
  • Methyltransferases
  • thiopurine methyltransferase
  • Thioguanine
  • Azathioprine