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


CONCLUSIONS
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.
Andoh
Akira
A
Department of Medicine, Shiga University of Medical Science, Seta Tukinowa, Japan. andoh@belle.shiga-med.ac.jp
Tsujikawa
Tomoyuki
T
Ban
Hiromitsu
H
Hashimoto
Takayoshi
T
Bamba
Shigeki
S
Ogawa
Atsuhiro
A
Sasaki
Masaya
M
Saito
Yasuharu
Y
Fujiyama
Yoshihide
Y
D000284:Administration, Oral; D001379:Azathioprine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D016903:Drug Monitoring / Q000379:methods*; D004906:Erythrocyte Count; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007564:Japan; D007958:Leukocyte Count; D015122:Mercaptopurine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016017:Odds Ratio; D012074:Remission Induction; D013866:Thioguanine / Q000097:blood*; D016896:Treatment Outcome
D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine