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Monitoring 6‐thioguanine nucleotide concentrations in Japanese children and adolescents with inflammatory bowel disease
Author(s) -
Ohtsuka Yoshikazu,
Arai Katsuhiro,
Aoyagi Yo,
Fujii Tohru,
Yamakawa Yoko,
Ohtani Kiyotaka,
Ikuse Tamaki,
Baba Yosuke,
Inage Eisuke,
Kudo Takahiro,
Suzuki Ryuyo,
Nagata Satoru,
Shimizu Toshiaki
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2010.06364.x
Subject(s) - medicine , thiopurine methyltransferase , ulcerative colitis , mercaptopurine , azathioprine , inflammatory bowel disease , gastroenterology , leukopenia , population , white blood cell , disease , chemotherapy , environmental health
Background and Aim: 6‐Mercaptopurine (6‐MP) and azathioprine (AZA) are widely used as maintenance therapy in children with inflammatory bowel disease (IBD). However, proper 6‐thioguanine nucleotide (6‐TGN) concentrations in Japanese children with IBD have not been reported. Methods: This retrospective review examines 32 ulcerative colitis (UC) patients and 19 Crohn's disease (CD) patients (12.87 ± 3.56 years) who required 6‐MP or AZA to maintain disease remission. All patients were treated with 6‐MP or AZA for at least 3 weeks prior to this study in addition to previous treatment. 6‐MP dose, 6‐TGN levels, assayed by high‐performance liquid chromatography, as well as laboratory data were evaluated. Results: Thirty‐five children were successfully kept in remission with 6‐MP and AZA therapy after weaning off corticosteroids. Overall, 123 measurements (59 active disease, 64 in remission) were analyzed. The mean 6‐TGN concentration of the entire study population was 499.61 ± 249.35 pmol/8 × 10 8 red blood cell. The mean 6‐MP dose in patients with active disease (0.910 ± 0.326 mg/kg per day) was significantly higher than for patients in remission (0.749 ± 0.225) ( P = 0.0016). A significant inverse correlation was found between white blood cell counts and 6‐TGN concentrations ( r = 0.275, P < 0.002). Two patients experienced leukopenia with alopecia, and four transiently experienced increased serum levels of pancreatic enzymes, although no thiopurine S‐methyl transferase mutations were confirmed. Conclusion: The doses of 6‐MP or AZA needed to maintain remission in Japanese children with IBD are lower than those reported in Western countries. However, 6‐TGN concentrations in this population are higher than previously reported.