Furugen, Ayako

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy ( Shiba-Kyoritsu )

Position

Associate Professor (Non-tenured)

Career 【 Display / hide

  • 2013.04
    -
    2015.06

    Hokkaido University, Hokkaido University Hospital

  • 2015.07
    -
    2023.03

    Hokkaido University, Faculty of Pharmaceutical Sciences

  • 2024.04
    -
    Present

    Keio University, Faculty of Pharmacy, Associate Professor

  • 2024.05
    -
    Present

    北海道大学, 大学院薬学研究院, 招へい教員(客員准教授)

Academic Background 【 Display / hide

  • 2004.04
    -
    2008.03

    Hokkaido University, Faculty of Pharmaceutical Sciences, 総合薬学科

    University, Graduated

  • 2008.04
    -
    2010.03

    Hokkaido University, Graduate School of Life Science, 生命医薬科学コース 修士課程

    Graduate School, Completed, Master's course

  • 2010.04
    -
    2013.03

    Hokkaido University, Graduate School of Life Science, 生命医薬科学コース 博士課程

    Graduate School, Completed, Doctoral course

Licenses and Qualifications 【 Display / hide

  • 薬剤師免許, 2008.04

 

Research Areas 【 Display / hide

  • Life Science / Clinical pharmacy

 

Papers 【 Display / hide

  • Evaluation of intestinal absorption of deoxyribonucleic acid components in salmon milt extract using in-situ and in vitro gastrointestinal absorption models.

    Taguchi R, Narumi K, Ueda H, Satoh H, Mori T, Okamoto K, Furugen A, Kobayashi M.

     2026.01

    Research paper (scientific journal), Joint Work, Accepted

  • Placental transfer of third-generation antiepileptic drugs: in vivo lacosamide case study and in vitro investigation of transporter inhibition by lacosamide and perampanel.

    Ueda A, Furugen A, Nishimura A, Umazume T, Aoyagi R, Okamoto K, Narumi K, Ueda H, Kobayashi M.

    J Pharm Health Care Sci.   2026.01

    Research paper (scientific journal), Joint Work, Corresponding author, Accepted

  • Validity and Utility of a Risk Prediction Model for Wound Infection After Lower Third Molar Surgery

    Akira Yamagami, Katsuya Narumi, Yoshitaka Saito, Ayako Furugen, Shungo Imai, Keisuke Okamoto, Yoshimasa Kitagawa, Yoichi Ohiro, Ryo Takagi, Yoh Takekuma, Mitsuru Sugawara, Masaki Kobayashi

    Oral Diseases (Wiley)  31 ( 6 ) 1922 - 1931 2025.06

    Research paper (scientific journal), Accepted,  ISSN  1354523X

     View Summary

    ABSTRACT

    Objectives

    To externally validate a clinical prediction model for surgical site infection (SSI) after lower third molar (L3M) surgery and evaluate its clinical usefulness.

    Methods

    We conducted a retrospective cohort study of patients who underwent L3M surgery at Hokkaido University Hospital. The study was designed to evaluate the historical and methodological transportability. Clinical usefulness was evaluated using decision curve analysis on the data of the non‐antibiotic‐treated patients.

    Results

    We obtained 2543 validation cohorts from April 2020 to March 2023, and 640 non‐antibiotic cohorts from July 2010 to September 2023. The incidences of SSI after L3M surgery were 5.3% (135/2543) and 7.7% (49/640) in the validation and non‐antibiotic cohorts, respectively. The discrimination ability of the prediction model was acceptable for the external validation cohort (c‐statistic: 0.67; 95% CI: 0.62–0.71) and adequate for the non‐antibiotic cohort (c‐statistic: 0.72; 95% CI: 0.63–0.79). In both cohorts, the model showed excellent calibration between the observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds.

    Conclusion

    A simple risk prediction model for SSI after L3M surgery demonstrated clinical transportability and usefulness. This model may help surgeons/clinicians determine the appropriateness of prophylactic antibiotics administration for patients in L3M surgery.

  • Analysis of drug transporter expression in syncytiotrophoblast derived from human placental stem cells: Expression and function of efflux transporters.

    Riko Sawada, Ayako Furugen, Ayami Ueda, Ayako Nishimura, Takeshi Umazume, Katsuya Narumi, Masaki Kobayashi

    Placenta 165   23 - 32 2025.05

    Research paper (scientific journal), Corresponding author, Accepted,  ISSN  01434004

     View Summary

    OBJECTIVE: The placenta is a vital organ for exchanging nutrients, endogenous substances, and xenobiotics between mother and fetus. The syncytiotrophoblast (ST) is crucial in maintaining the placental barrier. Human trophoblast stem cells (hTSCs) have been recently established; however, their utility in studying placental transport functions has not been fully elucidated. This study investigated the expression and function of transporters in hTSC-derived ST cells. METHODS: TSCT cells, as hTSCs, were differentiated into ST-like cells (ST-TSCT), and the gene expression of 84 transporters in ST-TSCT cells was evaluated using a PCR array. BeWo cells, a widely used trophoblast model, were used for comparison. BeWo cells were differentiated into ST-like cells using forskolin [BeWo (FK)]. The protein levels of efflux transporters were examined by western blotting, and functional assays were performed using typical fluorescent substrates. RESULTS: Transporter gene expression levels were higher in ST-TSCT than in BeWo (FK) cells, with 27 genes showing more than a 3-fold increase. Ten of these genes were exclusively expressed in ST-TSCT. Western blotting revealed the presence of efflux transporters, including P-glycoprotein (P-gp/ABCB1), breast cancer resistance protein (BCRP/ABCG2), and multidrug resistance-associated protein 2 (MRP2/ABCC2). Furthermore, the accumulation of typical substrates (Rhodamine123 for P-gp, Hoechst33342 and BODIPY™ FL Prazosin for BCRP, and 5(6)-carboxy-2',7'-dichlorofluorescein diacetate for MRP) significantly increased when transporter inhibitors (elacridar, Ko143, and MK571) were applied. CONCLUSION: This study showed higher transporter expression in ST-TSCT than that in a traditional trophoblast model. Furthermore, the functional expression of efflux transporters was observed. ST-TSCT is valuable for investigating placental transport functions.

  • Evaluation of the Effect of Aldehyde Oxidase Inhibitors on 6-Mercaptopurine Metabolism

    Ueda H., Narumi K., Furugen A., Okamoto K., Saito Y., Kobayashi M.

    Biological and Pharmaceutical Bulletin 48 ( 5 ) 713 - 720 2025.05

    Research paper (scientific journal), Accepted,  ISSN  09186158

     View Summary

    Thiopurines, such as 6-mercaptopurine (6-MP) and azathioprine, are converted to the inactive metabolites 6-thioxanthin (6-TX) and 6-thiouric acid (6-TUA). Molybdenum-containing oxidoreductases, aldehyde oxidase (AOX) and xanthine oxidase (XO), are involved in the oxidation of 6-MP to 6-TX; XO inhibitors affect the therapeutic efficacy of thiopurines and the incidence of adverse effects, such as liver and blood disorders. However, the role of AOX in the pharmacokinetics of 6-MP remains unclear. To clarify the clinical importance of AOX-mediated drug–drug interactions, we evaluated whether drugs that inhibit AOX affect 6-MP metabolism. The metabolism of 6-MP to 6-TX was strongly inhibited by AOX inhibitors (amitriptyline, chlorpromazine, clomipramine, clozapine, hydralazine, quetiapine, and raloxifene) in a reaction mixture containing human liver cytosol. The inhibition of 6-TX production rate by each AOX inhibitor was 60–70% at high concentrations, although the XO inhibitor febuxostat showed an inhibition rate of 10–30%. Furthermore, the combination of febuxostat and each AOX inhibitor showed greater inhibition than when each compound was added alone. The AOX inhibitor did not alter 6-MP oxidation by recombinant XO. These results suggest that AOX inhibition may affect the pharmacokinetics of thiopurines. However, because of the lower activity of AOX in rats than that in humans, the contribution of AOX could not be assessed using in vivo experiments. Further studies are needed to evaluate the contribution of AOX to the therapeutic and adverse effects of thiopurines, both in clinical studies and in animal models of liver humanization.

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Reviews, Commentaries, etc. 【 Display / hide

  • Reply to Accurate Risk Prediction Model for Surgical Site Infection After Lower Third Molar Surgery.

    Akira Yamagami, Katsuya Narumi, Yoshitaka Saito, Ayako Furugen, Shungo Imai, Yoshimasa Kitagawa, Yoichi Ohiro, Ryo Takagi, Yoh Takekuma, Mitsuru Sugawara, Masaki Kobayashi

    Oral diseases 31 ( 4 ) 1374 - 1375 2025.04

    ISSN  1354523X

  • オレキシン受容体拮抗薬のUPLC/MS/MS定量法構築とヒト乳汁移行性評価への応用

    石川 陽菜, 古堅, 彩子, 西村, あや子, 馬詰, 武, 青柳, 亮一, 石川, 修平, 鳴海, 克哉, 岡本, 敬介, 武隈, 洋, 菅原, 満, 小林 正紀

    日本TDM学会  2024.07

  • Functional analysis of hMCT2 involved in memory formation and the exploration of its high selective inhibitors

    山口敦史, 山口敦史, 向井悠斗, 佐久間智也, 岡本敬介, 古堅彩子, 鳴海克哉, 小林正紀

    日本薬学会年会要旨集(Web) 144th 2024

    ISSN  0918-9823

  • AOX1遺伝子の5’上流および3’非翻訳領域におけるSNP解析

    林愛, 鳴海克哉, 上田一奈太, 岡本敬介, 古堅彩子, 小林正紀

    TDM研究 41 ( 2 )  2024

    ISSN  0911-1026

  • メトトレキサート誘発性肝障害におけるアルデヒドオキシダーゼの寄与-基礎および薬剤疫学的アプローチによる検証-

    鳴海克哉, 森山綾子, 上田一奈太, 淺野秀峰, 古堅彩子, 小林正紀

    医療薬学フォーラム講演要旨集 31st 2023

    ISSN  1348-0863

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 母体痩せによる糖代謝物の母体-胎児間の動態変化と子への影響

    2024.08
    -
    2025.08

    一般財団法人 糧食研究会, 令和6年度(2024年)一般公募研究, Principal investigator

  • 周産期の安全な精神神経科系薬剤の服薬支援のためのエビデンス構築

    2024.04
    -
    2027.03

    日本学術振興会, 科学研究費助成事業, 基盤研究(B), No Setting

  • トロホブラスト分化マーカーを指標とした薬剤による胎児毒性の新規評価法の開発

    2023.11
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    2024.06

    横山臨床薬理研究助成基金, 令和5年度研究助成(一般研究助成), Principal investigator

  • 胎盤幹細胞由来syncytiotrophoblastを用いた薬物の胎盤通過性評価とメカニズムの解明

    2023.08
    -
    2025.03

    日本学術振興会, 科学研究費助成事業, 研究活動スタート支援, No Setting

  • 女性におけるVitamin D 状態の評価と胎盤機能との関連性

    2022.07
    -
    2023.06

    公益財団法人 三島海雲記念財団 2022年度 学術研究奨励金, Principal investigator

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Awards 【 Display / hide

  • 2024年度 日本薬学会賞女性薬学研究者奨励賞

    古堅 彩子, 2023

  • 2019年度 日本薬学会北海道支部 奨励賞 (医療系)

    古堅 彩子, 2019

  • 平成27 年度 Postdoctoral Award

    古堅 彩子, 2015, 日本医療薬学会

 

Courses Taught 【 Display / hide

  • THAI PHARMACY EXPERIENCE

    2025

  • STUDY OF MAJOR FIELD (HEALTHCARE INNOVATION IN PHARMACY)

    2025

  • SEMINAR(HEALTHCARE INNOVATION IN PHARMACY)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • PRIOR LEARNING FOR CLINICAL PRACTICE 5

    2025

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Committee Experiences 【 Display / hide

  • 2023.06
    -
    2024.03

    北海道薬剤師会, 学術・情報委員会委員

  • 2022.07
    -
    Present

    日本薬学会医療薬科学部会, 若手世話人