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Research on the movement of antidotes and toxic metabolites in the patients with acetaminophen poisoning

Research Project

Project/Area Number 13671623
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKansai Medical University

Principal Investigator

KIRIDOSHI Masaya  Kansai Medical University, Faculty of Medicine., Instructor, 医学部, 助手 (10330185)

Co-Investigator(Kenkyū-buntansha) KOMIYAMA Yutaka  Kansai Medical University, Faculty of Medicine., Assistant Professor, 医学部, 講師 (40140264)
NAKATANI Toshio  Kansai Medical University, Faculty of Medicine., Professor, 医学部, 教授 (70188978)
SHINYA Hiroshi  Kansai Medical University, Faculty of Medicine., Instructor, 医学部, 助手 (90309229)
TAKAHASHI Hakuo  Kansai Medical University, Faculty of Medicine., Professor, 医学部, 教授 (80094431)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsacetaminophen / N-acetylcysteine / N-acetyl-p-benzoquinone imine / poisoning / HPLC / LC / MS / Nアセチルベンゾキノンイミン / LCMS / 肝ミトコンドリア / AKBR
Research Abstract

Acetaminophen is widely used as an analgesic and antipyretic drug instead of aspirin. As it is contained in most flu drugs that are on the market, it can easily be obtained. It is widely noticed that a relatively small dose of acetaminophen can cause a fatal hepatic darangement. Acetaminophen itself is not toxic, but its intermediate metabolite N-acetyl-p-benzoquinone imine (NAPQI) is known to be toxic. When reduced glutathion, an activated compound, is depleted, NAPQI irreversibly binds with various kinds of protein in the liver, and hence it is hepatotoxic.
We investigated to detect the blood concentration of NAPQI with liquid chromatography! mass spectroscopy, and have gotten important findings. That is, asNAPQI promptly combines with activated-SH and is a highly unstable compound, it is impossible to detect it directly. However, we found that NAPQI covalently bond with GSH(GS-APAP) can relatively easily be detected by Liquid Chromatography /Mass Spectrogrphy (LCIMS). We also tried to detect the NAC (N-acetyl-cysteine) with LCIMS, and succeeded to detect the specific signal of mass spectrogram.
When patients are admitted due to overdose of acetaminophen, its blood concentrations were determined on admission and after the treatment with antidote. However, the number of patients admitted with the overdose was too small, and all the patients were not severe enough to be treated with blood purification. Hence, we could not determine the changes in the blood concentrations of acetaminophen and its metabolite serially. We determined the blood concentrations of acetaminophen before and after intragastric administration of antidotes in a few patients.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 堀 寧, 岩崎 泰昌, 黒木由美子, 小宮山豊, 中谷壽男, 他: "アセトアミノフェン"中毒研究. 15(4). 385-390 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中谷毒男, 新谷 裕, 原 克子, 小宮山豊, 高橋伯夫: "急性中毒における高度救命救急センターの役割"日本職業・災害医学会雑誌. 50(5). 331-334 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中谷壽男: "分析技術の救急医療への応用"医学のあゆみ. 203(12). 1027-1030 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 44. 1041-1064 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 45. 1099-1124 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 46. 1129-1154 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Atushi Hon, yasumasa Iwasaki, Yumiko Kuroki, Yutaka Komiyama, Toshio Nakatani, et al.: "Acetaminophen"Japanese Journal of Toxicology. 15-4. 385-390 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshio Nakatani, Yutaka Shinya, Katuko Hara, Yutaka Komiyama, Hakuo Takahashi: "Role of the emergency medical centers in acute poisoning."Japanese Journal of Occupational Medicine and Traumatology. 50-5. 331-334 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshio Nakatani: "Application of chemical analysis to the emergency medicine"Journall of Clinical and Experimental Medicine. 203-12 and 13. 1027-1030 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshio Nakatani, Yasuhiro Yamamoto: "Acute poisoning"Today's Therapy. 44. 1041-1064 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshio Nakatani, Yasuhiro Yamamoto: "Acute poisoning"Today's Therapy. 45. 1099-1124 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshio Nakatani, Yasuhiro Yamamoto: "Acute poisoning"Today's Therapy. 46. 1129-1154 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 堀 寧, 岩崎泰昌, 黒木由美子, 小宮山豊, 中谷壽男, 他: "アセトアミノフェン"中毒研究. 15(4). 385-390 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中谷壽男, 新谷 裕, 原 克子, 小宮山豊, 高橋伯夫: "急性中毒における高度救命救急センターの役割"日本職業・災害医学会雑誌. 50(5). 331-334 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 44. 1041-1064 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 45. 1099-1124 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 46. 1129-1154 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 堀 寧, 岩崎泰昌, 黒木由美子, 小宮山豊, 中谷壽男, 他: "アセトアミノフェン"中毒研究. 15(4). 385-390 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中谷壽男, 新谷 裕, 原 克子, 小宮山豊, 高橋伯夫: "急性中毒における高度救命救急センターの役割"日本職業・災害医学会. 50(5). 331-334 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中谷壽男, 山本保博: "急性中毒"今日の治療指針. 44. 1041-1064 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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