Monitoring 6-thioguanine nucleotide concentrations in Japanese children and adolescents with inflammatory bowel disease.
OBJECTIVE
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.


CONCLUSIONS
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.
Ohtsuka
Yoshikazu
Y
Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. yohtsuka@juntendo.ac.jp
Arai
Katsuhiro
K
Aoyagi
Yo
Y
Fujii
Tohru
T
Yamakawa
Yoko
Y
Ohtani
Kiyotaka
K
Ikuse
Tamaki
T
Baba
Yosuke
Y
Inage
Eisuke
E
Kudo
Takahiro
T
Suzuki
Ryuyo
R
Nagata
Satoru
S
Shimizu
Toshiaki
T
D000293:Adolescent; D001379:Azathioprine / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological / Q000097:blood*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy; D007564:Japan / Q000453:epidemiology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage*; D012074:Remission Induction; D012189:Retrospective Studies; D013873:Thionucleotides / Q000097:blood*; D016896:Treatment Outcome
D054316:Biomarkers, Pharmacological; D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D015122:Mercaptopurine; D001379:Azathioprine