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

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.

• Authors: Akira Andoh, Tomoyuki Tsujikawa, Hiromitsu Ban, Takayoshi Hashimoto, Shigeki Bamba, Atsuhiro Ogawa, Masaya Sasaki, Yasuharu Saito, Yoshihide Fujiyama
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 23 Issue 9 Pg. 1373-7 (Sep 2008) ISSN: 1440-1746 [Electronic] Australia
• PMID: 18662197 (Publication Type: Clinical Trial, Journal Article)

Chemical References

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

Topics

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