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The evaluation of risk of increased metal absorption and elucidation of novel mechanism associated with the drug-drug interaction by chelation.

Research Project

Project/Area Number 18K14957
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKeio University

Principal Investigator

Imaoka Ayuko  慶應義塾大学, 薬学部(芝共立), 助教 (10710957)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルミニウム / ニューキノロン系抗菌薬 / テトラサイクリン系抗菌薬 / キレート形成 / 消化管吸収 / 薬物相互作用 / 金属カチオン
Outline of Final Research Achievements

In this study, we evaluated the increased aluminum absorption associated with drug interaction caused by chelation. In the evaluation using gastrointestinal absorption model cells, it was shown that the effect of antimicrobial drug on aluminum absorption may be different between new quinolone antibiotics (NQs) and tetracycline antibiotics (TCs) which interact with metal cations by same mechanism. In the evaluation using the P-glycoprotein (P-gp) overexpression cells, it was revealed the chelate between levofloxacin and aluminum was not the substrate of P-gp.

Academic Significance and Societal Importance of the Research Achievements

アルミニウム (Al) は過剰摂取するとアルツハイマー病などの神経変性疾患につながるといわれている。本研究結果より、ニューキノロン系抗菌薬と Al を併用した際には、P 糖タンパク質によるキレート体の排出は期待できず、Al は脳へ移行する可能性が高いことが示唆された。つまり、両者併用時には Al の脳への蓄積が促進され、神経変性疾患の発症リスクが上昇する可能性を示唆できたことから、本研究成果は臨床的意義がある。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2019

All Presentation (1 results)

  • [Presentation] テトラサイクリンとアルミニウムの消化管上皮細胞単層膜透過と相互作用2019

    • Author(s)
      武田愛美、今岡鮎子、秋好健志、大谷壽一
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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