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Effect of Food on the Intestinal PEPT1-mediated Drug Absorption

Research Project

Project/Area Number 22590505
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionTakasaki University of Health and Welfare

Principal Investigator

MORIMOTO Kaori  高崎健康福祉大学, 薬学部, 講師 (90401009)

Co-Investigator(Kenkyū-buntansha) MORIMOTO Kaori  高崎健康福祉大学, 薬学部, 講師 (90401009)
OGIHARA Takuo  高崎健康福祉大学, 薬学部, 教授 (80448886)
KANO Takashi  高崎健康福祉大学, 薬学部, 助教 (70509257)
IDOTA Yoko  高崎健康福祉大学, 薬学部, 研究員 (90629594)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords医薬品副作用 / 薬物相互作用 / PEPT1 / 相互作用 / 消化管吸収 / トランスポーター / 薬物-食物間相互作用 / PEPT-1 / ミルク / 臨床試験 / 消化管吸
Research Abstract

In the present study, we found that oseltamivir, an ester-type prodrug of neuraminidase inhibitor [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene -1-carboxylic acid (Ro 64-0802), was effectively taken up by PEPT1 in vitro and that oseltamivir absorption in rats was greatly reduced by simultaneous administration of milk, casein , or glysylsarcosin. In addition, clinical stud iesin healthy volunteers showed that milk significantly reduced the maximum plasma concentrations (Cmax) and the area under the plasma concentration -time curves from 0 to 2 hour (AUC0-2) of both oseltamivir and Ro 64-0802. However, the extent of interaction was different between rats and humans, possibly because of sepecies difference in the PEPT1 expression and its contribution. Same interactions for known PEPT1 substrates were also seen in rat in vivo. These might be a first finding that suggests clinical drug-food interaction via PEPT1.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (30 results)

All 2013 2012 2011 2010

All Journal Article (12 results) (of which Peer Reviewed: 8 results) Presentation (18 results)

  • [Journal Article] 消化管吸収過程におけるペプチドトランスポーター・PEPT1 を介した薬物-食物間相互作用の解析2013

    • Author(s)
      森本かおり
    • Journal Title

      薬学研究の進歩 研究成果報告集

      Volume: 29巻 Pages: 87-91

    • Related Report
      2012 Final Research Report
  • [Journal Article] The Role of Inter-segmental Differences in P-glycoprotein expression and activityalong the rat small intestine in causing the double-peak phenomenon of substrate plasma concentration2013

    • Author(s)
      Wada S, Kano T, Mita S, Idota Y, Morimoto K, Yamashita F, Ogihara T.
    • Journal Title

      Drug Metab Pharmacokinet.

      Volume: Vo.28 Pages: 98-103

    • URL

      https://www.jstage.jst.go.jp/article/dmpk/28/2/28_DMPK-12-RG-005/_article

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 消化管吸収過程におけるペプチドトランスポーター・PEPT1を介した薬物-食物間相互作用の解析2013

    • Author(s)
      森本かおり
    • Journal Title

      薬学研究の進歩

      Volume: 29 Pages: 87-91

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Developmental changes of brain distribution and localization of oseltamivir and its active metabolite Ro 64-0802 in rats2012

    • Author(s)
      Morimoto K, Nagami T, Matsumoto N, Wada S, Kano T, Kakinuma, Ogihara T
    • Journal Title

      J Toxicol Sci

      Volume: Vol.37 Pages: 1217-1223

    • NAID

      10031126025

    • URL

      https://www.jstage.jst.go.jp/article/jts/37/6/37_1217/_pdf

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transport mechanism of flavanone aglycones across Caco-2 cell monolayers and artificial PAMPA membranes2012

    • Author(s)
      Kobayashi S, Nagai T, Konishi Y, Tanabe S, Morimoto K, Ogihara T
    • Journal Title

      J Pharm Pharmacol

      Volume: Vol.61 Issue: 1 Pages: 52-60

    • DOI

      10.1111/j.2042-7158.2011.01374.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Species difference of esterase expression and hydrolase activity in plasma2012

    • Author(s)
      Bahar F.G., Ohura K., Ogihara T., Imai T
    • Journal Title

      J. Pharm. Sci

      Volume: Vol. 101 Issue: 10 Pages: 3979-3988

    • DOI

      10.1002/jps.23258

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 有機アニオントランスポーターの遺伝子多型による前立腺がんの再燃予測2012

    • Author(s)
      森本かおり
    • Journal Title

      ファルマシア

      Volume: Vol.48 Pages: 556-556

    • NAID

      110009885212

    • Related Report
      2012 Final Research Report
  • [Journal Article] Developmental changes of brain distribution and localization of oseltamivir and its active metabolite Ro 64-0802 in rats.2012

    • Author(s)
      Kaori Morimoto
    • Journal Title

      J Toxicol Sci.

      Volume: 37 Pages: 1217-1223

    • NAID

      10031126025

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of milk on the pharmacokinetics of oseltamivir in healthy volunteers2011

    • Author(s)
      Morimoto K, Kishimura K, Nagami T, Kodama N, Ogama Y, Yokoyama M, Toda S, Chiyoda T, Shimada R, Inano A, Kano T, Tamai I, Ogihara T
    • Journal Title

      J. Pharm. Sci

      Volume: Vol.100 Issue: 9 Pages: 3854-3861

    • DOI

      10.1002/jps.22627

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 食品成分と薬物の相互作用2011

    • Author(s)
      小林彰子, 森本かおり, 荻原琢男
    • Journal Title

      BIOINDUSTRY

      Volume: 28巻 Pages: 30-35

    • URL

      http://www.fujisan.co.jp/product/1281680662/b/691304/

    • Related Report
      2012 Final Research Report
  • [Journal Article] 食品成分と薬物の相互作用2011

    • Author(s)
      小林彰子
    • Journal Title

      BIOINDUSTRY.

      Volume: 28 Pages: 30-35

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of milk on the pharmacokinetics of oseltamivir in healthy volunteers2011

    • Author(s)
      Kaori Morimoto
    • Journal Title

      J. Pharm. Sci

      Volume: 100 Pages: 3854-3861

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] グルコースと PEPT1 基質薬物の消化管吸収過程における相互作用2013

    • Author(s)
      一場紀子
    • Organizer
      日本薬剤学会第28 年会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-05-25
    • Related Report
      2012 Final Research Report
  • [Presentation] フラボノイドの胆汁酸腸管再吸収阻害機構の解析2013

    • Author(s)
      小川真奈
    • Organizer
      日本農芸化学会
    • Place of Presentation
      仙台
    • Year and Date
      2013-03-24
    • Related Report
      2012 Final Research Report
  • [Presentation] グルコースとPEPT1基質薬物の消化管吸収過程における相互作用2013

    • Author(s)
      一場紀子
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] Evaluation of a thiodipeptide, Ψ-Phe-Ala, as a PEPT1 probe to investigate of new PEPT1 substrate and inhibitors2012

    • Author(s)
      斎藤早知
    • Organizer
      第27回日本薬物動態学会年会
    • Place of Presentation
      千葉
    • Year and Date
      2012-11-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Oseltamivir 服用により精神症状をきたした一症例における薬物動態学的および薬理遺伝学的原因解析2012

    • Author(s)
      浅水秀明
    • Organizer
      第39回日本毒性学会
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Oseltamivir服用により精神症状をきたした一症例における薬物動態学的および薬理遺伝学的原因解析2012

    • Author(s)
      浅水秀明
    • Organizer
      第39回日本毒性学会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] Evaluation of a thiodipeptide, Ψ-Phe-Ala, as a PEPT1 probe to investigate of new PEPT1 substrates and inhibitors2012

    • Author(s)
      斎藤早知
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Related Report
      2012 Annual Research Report
  • [Presentation] Interaction of milk and oseltamivir on the intestinal PEPT1-mediated absorption in rats and humans2011

    • Author(s)
      岸 村 梢 江
    • Organizer
      第26回日本薬物動態学会年会
    • Place of Presentation
      広島
    • Year and Date
      2011-11-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Interaction of milk and oseltamivir on the intestinal PEPT1-mediated absorption in rats and humans.2011

    • Author(s)
      Kozue Kishimura
    • Organizer
      第26回 日本薬物動態学会年会
    • Place of Presentation
      広島
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Interaction of milk with the intestinal PEPT1-mediated absorption of oseltamivir in rats and humans2011

    • Author(s)
      Kaori Morimoto
    • Organizer
      17^NORTH AMERICAN MEETING OF ISSX
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2011-10-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Interaction of milk with the intestinal PEPT1-mediated absorption of oseltamivir in rats and humans.2011

    • Author(s)
      Kaori Morimoto
    • Organizer
      17^<th> NORTH AMERICAN MEETING OF lSSX
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2011-10-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] アムロジピンはペプチドトランスポーター1(PEPT1)の基質である2011

    • Author(s)
      当田達也
    • Organizer
      第55回日本薬学会関東支部大会 若手シンポジウム, F12
    • Place of Presentation
      船橋
    • Year and Date
      2011-10-08
    • Related Report
      2012 Final Research Report
  • [Presentation] オセルタミビルおよび活性代謝物 Ro64-0802 の脳内移行性および局在性の解析2011

    • Author(s)
      永見高輝
    • Organizer
      第38回日本トキシコロジー学会学術年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-07-11
    • Related Report
      2012 Final Research Report
  • [Presentation] オセルタミビルおよび活性代謝物Ro64-0802の脳内移行性および局在性の解析2011

    • Author(s)
      永見高輝
    • Organizer
      第38回日本トキシコロジー学会学術年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-07-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 消化管吸収過程における薬物とミルクのペプチドトランスポーター(PEPT1)を介した相互作用の解析2010

    • Author(s)
      小林彰子
    • Organizer
      日本薬剤学会第25 年会
    • Place of Presentation
      徳島
    • Year and Date
      2010-05-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 消化管吸収過程における薬物とミルクのペプチドトランスポーター(PEPT1)を介した相互作用の解析2010

    • Author(s)
      小林彰子
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール(徳島)
    • Year and Date
      2010-05-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] ペプチドトランスポーター(PEPT1)の基質となる薬物の消化管吸収に与えるミルクの影響2010

    • Author(s)
      我妻瑶恵
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2010-03-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] ペプチドトランスポーター(PEPT1)の基質となる薬物の消化管吸収に与えるミルクの影響2010

    • Author(s)
      我妻瑶恵
    • Organizer
      日本農芸化学会 2010 年度大会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-18
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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