Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients

Takako Komiyama, Tomoharu Yajima, Rie Kubota, Yasushi Iwao, Atsushi Sakuraba, Shinsuke Funakoshi, Kenichi Negishi, Ikuko Minami, Yoichi Tanaka, Hiroshi Mae, Toshifumi Hibi

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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 males; 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/8 × 108RBC, 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.

本文言語English
ページ(範囲)315-321
ページ数7
ジャーナルJournal of Crohn's and Colitis
2
4
DOI
出版ステータスPublished - 2008 12
外部発表はい

ASJC Scopus subject areas

  • 消化器病学

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