Details of a Researcher - Furugen, Ayako

Furugen, Ayako

写真a

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

Position: Associate Professor (Non-tenured)

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Career 【 Display / hide 】

2013.04

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2015.06

Hokkaido University, Hokkaido University Hospital
2015.07

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2023.03

Hokkaido University, Faculty of Pharmaceutical Sciences
2024.04

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Present

Keio University, Faculty of Pharmacy, Associate Professor

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Academic Background 【 Display / hide 】

2004.04

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2008.03

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

University, Graduated
2008.04

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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

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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

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Licenses and Qualifications 【 Display / hide 】

薬剤師免許, 2008.04

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Research Areas 【 Display / hide 】

Life Science / Clinical pharmacy

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Papers 【 Display / hide 】

Contribution of aldehyde oxidase to methotrexate-induced hepatotoxicity: In Vitro and pharmacoepidemiological approaches.

Ayako Moriyama, Hinata Ueda, Katsuya Narumi, Shuho Asano, Ayako Furugen, Yoshitaka Saito, Masaki Kobayashi

Expert opinion on drug metabolism & toxicology 2024.05

Research paper (scientific journal), Accepted

　View Summary

BACKGROUND: Methotrexate (MTX) is partially metabolized by aldehyde oxidase (AOX) in the liver and its clinical impact remains unclear. In this study, we aimed to demonstrate how AOX contributes to MTX-induced hepatotoxicity in vitro and clarify the relationship between concomitant AOX inhibitor use and MTX-associated liver injury development using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We assessed intracellular MTX accumulation and cytotoxicity using HepG2 cells. We used the FAERS database to detect reporting odds ratio (ROR)-based MTX-related hepatotoxicity event signals. RESULTS: AOX inhibition by AOX inhibitor raloxifene and siRNA increased the MTX accumulation in HepG2 cells and enhanced the MTX-induced cell viability reduction. In the FAERS analysis, the ROR for MTX-related hepatotoxicity increased with non-overlap of 95% confidence interval when co-administered with drugs with higher Imax, u (maximum unbound plasma concentration)/IC50 (half-maximal inhibitory concentration for inhibition of AOX) calculated based on reported pharmacokinetic data. CONCLUSION: AOX inhibition contributed to MTX accumulation in the liver, resulting in increased hepatotoxicity. Our study raises concerns regarding MTX-related hepatotoxicity when co-administered with drugs that possibly inhibit AOX activity at clinical concentrations.
- Access to Document (DOI)
Monocarboxylate Transporters 1 and 2 Are Responsible for L-Lactate Uptake in Differentiated Human Neuroblastoma SH-SY5Y Cells

Tomoya Sakuma, Yuto Mukai, Atsushi Yamaguchi, Yudai Suganuma, Keisuke Okamoto, Ayako Furugen, Katsuya Narumi, Shuhei Ishikawa, Yoshitaka Saito, Masaki Kobayashi

Biological and Pharmaceutical Bulletin （Pharmaceutical Society of Japan) 47 （ 4 ） 764 - 770 2024.04

Research paper (scientific journal), Accepted, ISSN 0918-6158
- Access to Document (DOI)
Breast milk concentrations of acetaminophen and diclofenac - unexpectedly high mammary transfer of the general-purpose drug acetaminophen.

Ryo Tamaki, Kiwamu Noshiro, Ayako Furugen, Ayako Nishimura, Hiroshi Asano, Hidemichi Watari, Masaki Kobayashi, Takeshi Umazume

BMC pregnancy and childbirth 24 （ 1 ） 90 - 90 2024.01

Research paper (scientific journal), Accepted

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BACKGROUND: Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques. METHODS: We conducted a study on 20 postpartum mothers from August 2019-March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach. RESULTS: For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093. CONCLUSIONS: While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.
- Access to Document (DOI)
Comparative study on the occurrence of adverse effects in the concomitant use of azathioprine and aldehyde oxidase inhibitors.

Hinata Ueda, Katsuya Narumi, Shuho Asano, Yoshitaka Saito, Ayako Furugen, Masaki Kobayashi

Expert opinion on drug safety 2023.12

Research paper (scientific journal), Accepted

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OBJECTIVES: Aldehyde oxidase (AO) is a molybdenum-containing redox enzyme similar to xanthine oxidase that is involved in the thiopurine metabolism. This study investigated the effects of drug-drug interactions (DDIs) between azathioprine (AZA) and AO inhibitors on hematologic and hepatic disorders using the U.S. Food and Drug Administration Adverse Event Reporting System and the Japanese Adverse Drug Event Report database. METHODS: The presence of DDI was assessed using the interaction signal scores (ISSs) calculated via the reporting odds ratios and 95% confidence intervals. The study used reports of 'azathioprine' as a suspect drug for adverse effects. AO inhibitors were selected based on previous in vitro reports. RESULTS: Some drugs tested positive for ISSs in each database and type of adverse effect (hematologic or hepatic disorder) analysis. Among these drugs, chlorpromazine, clozapine, hydralazine, and quetiapine could inhibit AZA metabolism via AO, given the previously reported clinical blood concentration and inhibitory effects of each drug. CONCLUSION: Concomitant use of AO inhibitors increased the signals for AZA-induced adverse effects. To date, no studies have evaluated the clinical importance of AO as a drug-metabolizing enzyme, and further in vitro and clinical research is needed to clarify the contribution of AO to the pharmacokinetics of thiopurines.
- Access to Document (DOI)
Use of lacosamide for focal epilepsy in a child with kidney failure undergoing peritoneal dialysis.

Yuki Ueda, Ayako Furugen, Masaki Kobayashi, Yasuyuki Sato, Yasuhiro Ueda, Asako Hayashi, Takeru Goto, Shuhei Kimura, Masashi Narugami, Sachiko Nakakubo, Midori Nakajima, Kiyoshi Egawa, Takayuki Okamoto, Atsushi Manabe, Hideaki Shiraishi

Brain & development 2023.10

Research paper (scientific journal), Accepted

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BACKGROUND: Lacosamide (LCM) has become commonly used for focal onset seizures due to its high tolerability and low drug interactions. Unlike patients on hemodialysis (HD), pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis (PD) are scant. CASE REPORT: A 2-year-old girl with end-stage kidney disease undergoing PD suffered prolonged focal onset seizures. The patient had congenital anomalies of the kidney and urinary tract associated with branchio-oto-renal syndrome due to an EYA1 gene mutation. She also had neurological sequelae from post-resuscitation encephalopathy at the age of one month. Antiseizure medication with few drug interactions, less impact on the neurodevelopmental state and possibility of intravenous administration was preferred. LCM met those criteria and was carefully administered. Although the patient had recurrent prolonged seizures during the titration periods, LCM could be continued without any apparent side effects. The blood levels of LCM increased linearly to the optimal level. We confirmed excretion of LCM in the PD fluid. Kidney transplantation was done three months after and her seizures were well controlled. CONCLUSIONS: LCM might be a promising option for patients undergoing PD. Due to the lower removal efficacy in PD compared with in HD, close attention should be paid to possible drug excess.
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Reviews, Commentaries, etc. 【 Display / hide 】

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
長時間作用型ベンゾジアゼピン(BZD)系薬のMilk/Plasma ratio(M/P比)およびRelative Infant Dose(RID)の算出

西村あや子, 古堅彩子, 馬詰武, 北村聖花, 武隈洋, 菅原満, 菅原満, 小林正紀

医療薬学フォーラム講演要旨集 31st 2023

ISSN 1348-0863
乳汁・血漿中lacosamideのUPLC/MS/MS定量法ならびに乳汁移行性評価への応用

古堅彩子, 西村あや子, 馬詰武, 石川陽菜, 鳴海克哉, 小林正紀

医療薬学フォーラム講演要旨集 31st 2023

ISSN 1348-0863
腹膜透析中に発症した焦点性てんかんに対してラコサミドを導入した小児例の経験

植田佑樹, 佐藤泰征, 林麻子, 上田泰弘, 木村修平, 後藤健, 中久保佐千子, 中島翠, 江川潔, 岡本孝之, 白石秀明, 古堅彩子, 小林正紀, 真部淳

てんかん研究 ((一社)日本てんかん学会) 40 ( 2 ) 467 - 467 2022.08

ISSN 0912-0890
歯科領域における経口第3世代セフェム系抗菌薬減少戦略の評価:中断時系列分析

山神彰, 鳴海克哉, 齋藤佳敬, 古堅彩子, 今井俊吾, 北川善政, 大廣洋一, 高木諒, 武隈洋, 菅原満, 菅原満, 小林正紀, 小林正紀

医療薬学フォーラム講演要旨集 30th 2022

ISSN 1348-0863

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

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

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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

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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
不眠に対するセルフメディケーションを見据えた睡眠薬の乳汁移行に関する研究

2022.06

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2023.03

公益財団法人一般用医薬品セルフメディケーション振興財団令和4年度(2022年) 調査・研究助成, Principal investigator
妊娠期酸化ストレス制御を指向した、抗酸化物質の胎盤移行および機能の多面的評価

2022.06

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2023.03

一般財団法人旗影会, 2022 年度旗影会研究助成, Principal investigator