Journal
JOURNAL OF CROHNS & COLITIS
Volume 2, Issue 4, Pages 315-321Publisher
OXFORD UNIV PRESS
DOI: 10.1016/j.crohns.2008.05.002
Keywords
6-Mercaptopurine; Azathioprine; 6-TGN level; Inflammatory bowel disease; Japanese patients
Categories
Funding
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Japanese Ministry of Health, Labor and Welfare
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Background: Although 6-mercaptopurine (6-MP) and azathioprine (AZA) are prescribed at lower doses, their efficacy in patients with inflammatory bowel disease (IBD) in Japan is comparable to that in Europe/America. However, there has been no report concerning the measurement of erythrocyte 6-thioguanine nucleotides (6-TGN), which is an active metabolite of 6-MP or AZA, in Japanese IBD patients. This study was designed to elucidate the pharmacokinetic-pharmacodynamic properties of 6-MP and AZA in Japanese patients by measurement of erythrocyte 6-TGN level. Methods: 134 adult patients (99 mates; 35 females) with IBD (75 ulcerative colitis; 59 Crohn's disease) who had been receiving a constant dose of 6-MP or AZA for three months or longer were enrolled. Erythrocyte 6-TGN levels were measured using the low-pressure gradient HPLC method, and correlated with treatment efficacy. The genetic polymorphism of thiopurine methyltransferase (TPMT) genotype was also assessed. Results: The mean erythrocyte 6-TGN level (mean +/- SD) was 342.3 +/- 220.9 pmol/8x10(8)RBC, which was supposed to be therapeutic concentration, although the mean daily doses of 6-MP and AZA were no more than 29.8 +/- 9.9 mg/day of 6-MP equivalent. However, all patients were identified with the wild type of TPMT genotype. There was no significant difference in the mean 6-TGN levels between patients in remission and no-remission group. The mean 6-TGN level was significantly higher in the once-daily administration group than three times-daily group. Conclusion: Thirty mg/day of 6-MP or 50 mg/day of AZA, once-daily oral administration in Japanese IBD patients was sufficient to achieve the therapeutic target level of 6-TGN in Europeans/Americans. (C) 2008 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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