Prediction of 6-thioguanine nucleotides levels in Japanese patients with inflammatory bowel diseases during long-term thiopurine administration

Scand J Gastroenterol. 2010 May;45(5):608-14. doi: 10.3109/00365521003642559.

Abstract

Background: The monitoring of 6-thioguanine nucleotides (6-TGN) levels is warranted during thiopurine therapy for patients with inflammatory bowel diseases.

Aims: The aim of this study was to elucidate the parameters that can predict the 6-TGN levels among Japanese patients with inflammatory bowel diseases undergoing thiopurine therapy.

Material and methods: The 6-TGN levels were measured in 54 patients with inflammatory bowel diseases (32 with ulcerative colitis and 22 with Crohn's disease), who had been administered azathioprine or 6-mercaptopurine for more than 90 days. Possible correlations between the hematologic parameters and 6-TGN levels were investigated. The clinical and hematologic variables were evaluated to determine the 6-TGN levels of less than or over 235 pmol/8 x 10(8) RBCs.

Results: The 6-TGN levels correlated significantly with changes in the mean corpuscular volume (R = 0.423, p = 0.001) and the lymphocyte counts (R = -0.280, p = 0.04). A multivariate analysis revealed changes in the mean corpuscular volume (OR: 1.22, 95% CI: 1.07-1.40) and hemoglobin levels (OR: 0.59, 95% CI: 0.35-0.99) to be factors predictive of the 6-TGN levels. An increase in the mean corpuscular volume of 3.5 fl was determined to be the most preferable cut-off value to distinguish patients with 6-TGN >or= 235 pmol/8 x 10(8) RBCs from those with a lower concentration.

Conclusions: Changes in the mean corpuscular volume are considered to be predictive of the 6-TGN levels in patients with inflammatory bowel diseases receiving thiopurine therapy.

MeSH terms

  • Adult
  • Azathioprine / administration & dosage*
  • Biomarkers, Pharmacological / blood
  • Chi-Square Distribution
  • Erythrocyte Volume
  • Female
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Japan
  • Logistic Models
  • Male
  • Mercaptopurine / administration & dosage
  • Nucleotides / blood*
  • Predictive Value of Tests
  • Retrospective Studies
  • Statistics, Nonparametric
  • Thioguanine / blood*

Substances

  • Biomarkers, Pharmacological
  • Nucleotides
  • Mercaptopurine
  • Thioguanine
  • Azathioprine