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Transport mechanism of antiepileptic drugs in the placenta and multidirectional approaches for risk reduction to the fetus

Research Project

Project/Area Number 16K18929
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionHokkaido University

Principal Investigator

FURUGEN Ayako  北海道大学, 薬学研究院, 助教 (90767261)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords抗てんかん薬 / 胎盤 / トランスポータ / ガバペンチン / ラモトリギン / バルプロ酸 / 葉酸 / 新規抗てんかん薬 / 医療系薬学
Outline of Final Research Achievements

The aim of the present study was to investigate the mechanism of antiepileptic drug transport across the placenta to reduce their risk to the fetus. The accumulated amounts of antiepileptic drugs in the placental cells were in the order, gabapentin > lamotrigine > levetiracetam > topiramate. We concluded that the influx of gabapentin, lamotrigine, and valproate into the placental cells was transporter-mediated. Furthermore, an experiment using transporter inhibitors and siRNAs indicated that L-type amino acid transporter 1 (LAT1) largely contributed to the transport of gabapentin into the placental cells.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Valproic acid transport in the choriocarcinoma placenta cell line JEG-3 proceeds independently of the proton-dependent transporters MCT1 and MCT42018

    • Author(s)
      Yuri Ishiguro, Ayako Furugen, Katsuya Narumi, Ayako Nishimura, Takeshi Hirano, Masaki Kobayashi, Ken Iseki.
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 印刷中 Issue: 6 Pages: 270-274

    • DOI

      10.1016/j.dmpk.2018.03.004

    • NAID

      210000170209

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of L-type amino acid transporter 1 in the transport of gabapentin into human placental choriocarcinoma cells.2017

    • Author(s)
      Furugen A, Ishiguro Y, Kobayashi M, Narumi K, Nishimura A, Hirano T, Iseki K.
    • Journal Title

      Reproductive Toxicology

      Volume: 67 Pages: 48-55

    • DOI

      10.1016/j.reprotox.2016.11.002

    • NAID

      120006727626

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 胎盤細胞への葉酸輸送に及ぼす抗てんかん薬の影響の評価2018

    • Author(s)
      黒澤 優子, 古堅 彩子, 西村 あや子, 鳴海 克哉, 小林 正紀, 井関 健
    • Organizer
      日本薬学会 第138年会 (金沢)
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト胎盤絨毛癌由来JEG-3 細胞におけるバルプロ酸の輸送機構2017

    • Author(s)
      石黒 由梨, 古堅 彩子, 西村 あや子, 小林 正紀, 鳴海 克哉, 井関 健
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台国際センター (宮城県 仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 母体―胎児間および母体―乳児間の物質輸送に着目した、 中枢神経系用薬の適正使用に向けた研究2017

    • Author(s)
      古堅 彩子
    • Organizer
      第1回 薬学会北海道支部主催 若手シンポジウム (札幌)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Involvement of L-type amino acid transporter 1 in the transport of gabapentin into human placental choriocarcinoma cells2017

    • Author(s)
      Ayako Furugen, Yuri Ishiguro, Masaki Kobayashi, Katsuya Narumi, Ayako Nishimura, Ken Iseki.
    • Organizer
      2017 紫禁城国際薬剤師フォーラム (北京)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] THE TRANSPORT MECHANISM OF NEWER ANTIEPILEPTIC DRUGS IN PLACENTAL CELLS : INVOLVEMENT OF L-TYPE AMINO ACID TRANSPORTER 1 IN THE TRANSPORT OF GABAPENTIN2016

    • Author(s)
      Furugen A, Ishiguro Y, Kobayashi M, Narumi K, Nishimura A, Iseki K.
    • Organizer
      日本薬物動態学会 第31回年会
    • Place of Presentation
      キッセイ文化ホール (長野県 松本市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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