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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)315-321
Number of pages7
JournalJournal of Crohn's and Colitis
Volume2
Issue number4
DOIs
Publication statusPublished - 2008 Dec
Externally publishedYes

Fingerprint

6-Mercaptopurine
Azathioprine
Inflammatory Bowel Diseases
Erythrocytes
thiopurine methyltransferase
Therapeutics
Genotype
Genetic Polymorphisms
6-thioguanylic acid
Ulcerative Colitis
Crohn Disease
Oral Administration
Japan
Pharmacokinetics
High Pressure Liquid Chromatography
Pressure

Keywords

  • 6-Mercaptopurine
  • 6-TGN level
  • Azathioprine
  • Inflammatory bowel disease
  • Japanese patients

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients. / Komiyama, Takako; Yajima, Tomoharu; Kubota, Rie; Iwao, Yasushi; Sakuraba, Atsushi; Funakoshi, Shinsuke; Negishi, Kenichi; Minami, Ikuko; Tanaka, Yoichi; Mae, Hiroshi; Hibi, Toshifumi.

In: Journal of Crohn's and Colitis, Vol. 2, No. 4, 12.2008, p. 315-321.

Research output: Contribution to journalArticle

Komiyama, Takako ; Yajima, Tomoharu ; Kubota, Rie ; Iwao, Yasushi ; Sakuraba, Atsushi ; Funakoshi, Shinsuke ; Negishi, Kenichi ; Minami, Ikuko ; Tanaka, Yoichi ; Mae, Hiroshi ; Hibi, Toshifumi. / Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients. In: Journal of Crohn's and Colitis. 2008 ; Vol. 2, No. 4. pp. 315-321.
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abstract = "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.",
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T1 - Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients

AU - Komiyama, Takako

AU - Yajima, Tomoharu

AU - Kubota, Rie

AU - Iwao, Yasushi

AU - Sakuraba, Atsushi

AU - Funakoshi, Shinsuke

AU - Negishi, Kenichi

AU - Minami, Ikuko

AU - Tanaka, Yoichi

AU - Mae, Hiroshi

AU - Hibi, Toshifumi

PY - 2008/12

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N2 - 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.

AB - 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.

KW - 6-Mercaptopurine

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KW - Azathioprine

KW - Inflammatory bowel disease

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