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

-

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）

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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

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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 】

Validated UPLC-MS/MS method for quantification of melatonin receptor agonists and dual orexin receptor antagonists in human plasma and breast milk: Application to quantify suvorexant and lemborexant in clinical samples

Hina Ishikawa, Ayako Furugen, Ayako Nishimura, Takeshi Umazume, Shuhei Ishikawa, Ryoichi Aoyagi, Katsuya Narumi, Keisuke Okamoto, Yoh Takekuma, Mitsuru Sugawara, Masaki Kobayashi

Journal of Pharmaceutical and Biomedical Analysis (Elsevier BV) 251 116432 - 116432 2024.12

Research paper (scientific journal), Corresponding author, Accepted, ISSN 0731-7085
- Access to Document (DOI)
Effects of famotidine use during pregnancy: an observational cohort study.

Ayako Nishimura, Ayako Furugen, Masaki Kobayashi, Yoh Takekuma, Naho Yakuwa, Mikako Goto, Masahiro Hayashi, Atsuko Murashima, Mitsuru Sugawara

Journal of pharmaceutical health care and sciences 10 ( 1 ) 70 - 70 2024.12

Research paper (scientific journal), Accepted

　View Summary

BACKGROUND: Famotidine, a histamine2-receptor antagonist (H2Ras), is widely used to treat and prevent gastrointestinal symptoms during pregnancy. Although several studies have reported the use of H2Ras during pregnancy, limited data on famotidine were included in these reports. Therefore, we analyzed pregnancy outcome data to evaluate the effects of famotidine use during pregnancy on the fetus. METHODS: Pregnancy outcome data were used for females enrolled in two Japanese facilities that provided counseling on drug use during pregnancy between April 1988 and December 2017. For the primary endpoint, the incidence of congenital malformations was calculated from the data of live birth to pregnant women who took famotidine (n = 330) or drugs considered to exert no teratogenic risk (control, n = 1,407) during the first trimester of pregnancy. Considering secondary endpoints, the incidence of obstetric outcomes, including preterm delivery, was calculated from data on the use of famotidine (n = 347) and controls (n = 1,476) during the entire pregnancy. The crude odds ratios (cORs) for the incidence of congenital malformations were calculated using univariate logistic regression analysis, with the control group used as the reference. Adjusted ORs (aORs) were calculated using multivariate logistic regression analysis adjusted for various other factors. RESULTS: The incidences of congenital malformations in the famotidine and control groups were 3.9% and 2.8%, respectively. There was no significant difference between the famotidine and control groups (cOR: 1.40 [95% CI:0.68-2.71], aOR: 1.06 [95% CI:0.51-2.16]). Conversely, the preterm delivery rates were 8.1% and 3.8% in the famotidine and control groups, respectively, indicating a significant difference (cOR: 2.00 [95% CI:1.20-3.27]). However, the multivariate analysis eliminated famotidine use as a confounding factor. CONCLUSIONS: This observational cohort study revealed that exposure to famotidine during the first trimester of pregnancy was not associated with an increased risk of congenital malformations in infants. Although a higher rate of preterm delivery was detected in famotidine users when compared with controls, this could be attributed to confounding factors, such as complications.
- Access to Document (DOI)
Association Between Multisystem Immune-related Adverse Events and Progression-free Survivals in PD-1/PD-L1 Inhibitor Monotherapy.

Atsushi Yamaguchi, Yoshitaka Saito, Keisuke Okamoto, Ayako Furugen, Katsuya Narumi, Yoh Takekuma, Jun Sakakibara-Konishi, Yasushi Shimizu, Ichiro Kinoshita, Mitsuru Sugawara, Masaki Kobayashi

In vivo (Athens, Greece) 38 ( 6 ) 2886 - 2896 2024.11

Research paper (scientific journal), Accepted, ISSN 0258851X

　View Summary

BACKGROUND/AIM: Immune-related adverse events (irAEs) occur in various organs, and sometimes multiply following treatment with immune checkpoint inhibitors (ICIs). This study aimed to determine the association between the number of irAEs and clinical outcomes. PATIENTS AND METHODS: This was a retrospective study that included patients with lung cancer, melanoma, and head and neck cancer who were treated with anti-programmed cell death (ligand) 1 (PD-1/PD-L1) monotherapy. We evaluated the association between the number of irAEs and progression-free survival (PFS) in the simple Cox regression analysis. To eliminate the immortal-time bias, an additional landmark analysis was performed. RESULTS: In total, 92, 69, and 37 patients were allocated to the no, single, and multisystem irAEs groups, respectively. The multisystem irAEs were associated with better PFS compared to the no irAE group. In contrast, at the 12-week landmark, multisystem irAEs were associated with poor PFS compared to the no irAEs group. Furthermore, the rate of treatment suspension owing to irAEs in the multisystem irAEs group (62.5%) was higher than that in the single irAE group (17.3%) at the 12-week landmark. CONCLUSION: The incidence of multisystem irAEs was associated with improved clinical outcomes in patients with lung cancer, melanoma, and head and neck cancer treated with PD-1/PD-L1 inhibitor monotherapy. However, these results may be influenced by a potential immortal-time bias. When accounting for this bias, the early development of multisystem irAEs within 12 weeks was linked to treatment suspension and poorer clinical outcomes.
- Access to Document (DOI)
Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells.

Yuki Miyazawa, Ayako Furugen, Ryoichi Aoyagi, Haruna Kosugi, Ayako Nishimura, Takeshi Umazume, Katsuya Narumi, Masaki Kobayashi

Toxicology in vitro : an international journal published in association with BIBRA 105934 - 105934 2024.09

Research paper (scientific journal), Corresponding author, Accepted

　View Summary

Folates are essential nutrients for fetal development during pregnancy. Valproic acid (VPA), an inhibitor of histone deacetylases (HDACs), alters the expression of folate carriers in placental cells; however, the underlying mechanisms remain unclear. Here, we aimed to determine the profiles of folate carriers (folate receptor alpha [FOLR1], solute carrier [SLC]-19A1, and SLC46A1) after inhibition of HDACs, especially class I and IIa HDACs, using different inhibitors and gene knockdown tests. Quantitative polymerase chain reaction revealed that BeWo cells (a trophoblast model) expressed HDACs and folate carriers, similar to human placental villi. FOLR1 expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. VPA and apicidin upregulated the expression of SLC46A1. These inhibitors downregulated SLC19A1 expression. TMP269 (a class IIa inhibitor) did not affect folate carrier levels. HDAC1/2 knockdown upregulated FOLR1 and SLC46A1 levels, whereas HDAC1/3 knockdown downregulated FOLR1 levels. Our findings suggest that the pharmacological inhibition of class I HDACs alters the expression of folate carriers in BeWo cells. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering FOLR1 and SLC46A1 levels.
- Access to Document (DOI)
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

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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)

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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