Nishimura, Tomohiro

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 薬剤学講座 （Shiba-Kyoritsu）

Position

Associate Professor

External Links
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Career 【 Display / hide 】

  • 2007.04
    -
    2008.03

    共立薬科大学, 助手

  • 2008.04
    -
    2013.03

    慶應義塾大学, 薬学部, 助教

  • 2011.09
    -
    2012.08

    Mount Sinai School of Medicine, Visiting Scientist

  • 2014.04
    -
    2017.03

    慶應義塾大学, 薬学部, 専任講師

  • 2017.04
    -
    Present

    慶應義塾大学, 薬学部, 准教授

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Academic Background 【 Display / hide 】

  • 2007.03

    Kanazawa University

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（薬学）, Kanazawa University, Coursework, 2007.03

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Licenses and Qualifications 【 Display / hide 】

  • 甲種危険物取扱者, 2000.12

  • 薬剤師, 2004.04

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Books 【 Display / hide 】

  • 今日のOTC薬　改訂第５版

    伊東明彦, 中村智徳（編集）西村友宏., 南江堂, 2021.02

    Scope: 31 ビタミン剤,  Contact page： 532-549

  • 別冊Newton　くすりの科学知識　増補第2版

    中島恵美,西村友宏(監修）., ニュートンプレス, 2019.10

    Contact page： 140-169

  • わかりやすい薬物動態計算問題の解き方

    丸山一雄（監修）中瀬朋夏（編集）西村友宏., ネオメディカル, 2019.03

    Scope: ６．未変化体の尿中排泄量と消失速度定数７．経口投与後の血中濃度推移と吸収速度定数,  Contact page： 29-41

  • 今日のOTC薬　改訂第４版

    中島恵美(監修）, 伊東明彦(編集）西村友宏., 南江堂, 2018.04

    Scope: 31 ビタミン剤,  Contact page： 528-547

  • 今日のOTC薬　改訂第３版

    中島恵美, 伊東明彦(編集）西村友宏., 南江堂, 2015.03

    Scope: 31 ビタミン剤,  Contact page： 546-567

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Papers 【 Display / hide 】

  • L-type Amino Acid Transporter 1 (SLC7A5)-Mediated Transport of Pregabalin at the Rat Blood-Spinal Cord Barrier and its Sensitivity to Plasma Branched-Chain Amino Acids.

    Akashi T, Noguchi S, Takahashi Y, Nishimura T, Tomi M

    Journal of pharmaceutical sciences （Journal of Pharmaceutical Sciences)  112 （ 4 ） 1137 - 1144 2023.01

    ISSN  0022-3549

    　View Summary

    Pregabalin is an anti-neuropathic pain drug inhibiting the α2δ subunit of the voltage-dependent calcium channel in the spinal cord. The aim of this study is to characterize the transport mechanism of pregabalin at the blood-spinal cord barrier (BSCB) by means of in vivo experiments in rats and in vitro studies using primary-cultured rat spinal cord endothelial cells. We isolated endothelial cells by culturing rat spinal cord tissue in the presence of puromycin, and confirmed the expression of BSCB markers such as Cd31, Mdr1a, and Claudin-5. The uptake of pregabalin by primary-cultured rat spinal cord endothelial cells was sodium-independent and was significantly inhibited by L-leucine, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, and JPH203. These results suggest the involvement of L-type amino acid transporter (LAT) 1. LAT1 mRNA and protein was expressed in primary-cultured rat spinal cord endothelial cells, which is consistent with LAT1 expression at the BSCB. In the in vivo study, the transfer of pregabalin to rat spinal cord and brain was significantly decreased by the pre-administration of branched chain amino acids (BCAAs), which are endogenous substrates of LAT1. Our results indicate that pregabalin transport across the BSCB is mediated at least in part by LAT1 and is inhibited by plasma BCAAs.

  • Quantitative comparison of breast cancer resistance protein (BCRP/ABCG2) expression and function between maternal blood-brain barrier and placental barrier in mice at different gestational ages

    Fujita A, Noguchi S, Hamada R, Shimada T, Katakura S, Maruyama T, Sai Y, Nishimura T, Tomi M

    Front Drug Deliv 2   932576 2022.07

    Research paper (scientific journal), Joint Work, Accepted

  • Limited Impact of Murine Placental MDR1 on Fetal Exposure of Certain Drugs Explained by Bypass Transfer Between Adjacent Syncytiotrophoblast Layers.

    Fujita A, Noguchi S, Hamada R, Inoue S, Shimada T, Katakura S, Maruyama T, Sai Y, Nishimura T, Tomi M

    Pharmaceutical research （Pharmaceutical Research)  39 （ 7 ） 1645 - 1658 2022.01

    Research paper (scientific journal), Accepted,  ISSN  0724-8741

    　View Summary

    Purpose: Multidrug resistance protein 1 (MDR1) is located at the interface between two syncytiotrophoblast layers in rodent placenta, and may influence fetal drug distribution. Here, we quantitatively compare the functional impact per single MDR1 molecule of MDR1 at the placental barrier and blood-brain barrier in mice. Methods: MDR1A and MDR1B proteins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Paclitaxel or digoxin was continuously administered to pregnant Mdr1a−/−/Mdr1b−/− or wild-type mice, and the drug concentrations in the maternal and fetal plasma and maternal brain were quantified by LC-MS/MS. Results: MDR1A and MDR1B proteins are expressed in the membrane of mouse placental labyrinth, and total MDR1 at the placental barrier amounts to about 30% of that at the blood-brain barrier. The fetal-to-maternal plasma concentration ratio of digoxin was only marginally affected in Mdr1a−/−/Mdr1b−/− mice, while that of paclitaxel showed a several-fold increase. No such difference between the two drugs was found in the maternal brain distribution. The impact per single MDR1 molecule on the fetal distribution of digoxin was calculated to be much lower than that on the brain distribution, but this was not the case for paclitaxel. Our pharmacokinetic model indicates that the impact of placental MDR1 is inversely correlated to the ratio of permeability through gap junctions connecting the two syncytiotrophoblast layers to passive diffusion permeability. Conclusion: Our findings indicate that murine placental MDR1 has a minimal influence on the fetal concentration of certain substrates, such as digoxin, due to bypass transfer, probably via connexin26 gap junctions.

  • Transplacental pharmacokinetic model of digoxin based on <i>ex vivo</i> human placental perfusion study.

    Kurosawa K, Noguchi S, Nishimura T, Tomi M, Chiba K

    Drug metabolism and disposition: the biological fate of chemicals （Drug Metabolism and Disposition)  50 （ 3 ） 287 - 298 2021.12

    Accepted,  ISSN  0090-9556

    　View Summary

    Digoxin is used as first-line therapy to treat fetal supraventricular tachycardia; however, because of the narrow therapeutic window, it is essential to estimate digoxin exposure in the fetus. The data from ex vivo human placental perfusion study are used to predict in vivo fetal exposure noninvasively, but the ex vivo fetal-to-maternal concentration (F:M) ratios observed in digoxin perfusion studies were much lower than those in vivo. In the present study, we developed a human transplacental pharmacokinetic model of digoxin using previously reported ex vivo human placental perfusion data. The model consists of maternal intervillous, fetal capillary, non-perfused tissue, and syncytiotrophoblast compartments, with multidrug resistance protein (MDR) 1 and influx transporter at the microvillous membrane (MVM) and influx and efflux transporters at the basal plasma membrane (BM). The model-predicted F:M ratio was 0.66, which is consistent with the mean in vivo value of 0.77 (95% confidence interval: 0.64-0.91). The time to achieve the steady state from the ex vivo perfusion study was estimated as 1,500 minutes, which is considerably longer than the reported ex vivo experimental durations, and this difference is considered to account for the inconsistency between ex vivo and in vivo F:M ratios. Reported digoxin concentrations in a drug-drug interaction study with MDR1 inhibitors quinidine and verapamil were consistent with the profiles simulated by our model incorporating inhibition of efflux transporter at the BM in addition to MVM. Our modeling and simulation approach should be a powerful tool to predict fetal exposure and DDIs in human placenta. SIGNIFICANCE STATEMENT We developed a human transplacental pharmacokinetic model of digoxin based on ex vivo human placental perfusion studies in order to resolve inconsistencies between reported ex vivo and in vivo fetal-to-maternal concentration ratios. The model successfully predicted the in vivo fetal exposure to digoxin and the drug-drug interactions of digoxin and P-glycoprotein/multidrug resistance protein 1 inhibitors in human placenta.

  • MicroRNA-126 suppresses the invasion of trophoblast-model JEG-3 cells by targeting LIN28A.

    Pan X, Noguchi S, Ando M, Nishimura T, Tomi M

    Biochemical and biophysical research communications （Biochemical and Biophysical Research Communications)  545   132 - 137 2021.03

    Accepted,  ISSN  0006-291X

    　View Summary

    Inadequate trophoblast invasion and impaired trophoblast-induced vascular remodeling are features of preeclampsia. In this context, an angiogenesis-related microRNA, miR-126, is abnormally expressed in preeclampsia placentas, but its role in trophoblast development remains unclear. The purpose of this study was to investigate the roles of miR-126 in the proliferation, migration, and invasion processes of trophoblast cells using the human choriocarcinoma-derived JEG-3 cell line as a model. The mRNA expression profiling of JEG-3 cells with and without miR-126 overexpression, in combination with bioinformatics analysis, identified LIN28A as a putative target of miR-126. The results of real-time RT-PCR and luciferase assay were consistent with this idea. Overexpression of miR-126 in JEG-3 cells decreased the invasive ability of the cells without affecting proliferation or migration. The invasiveness of JEG-3 cells was significantly reduced to a similar extent by knockdown of LIN28A with siRNA and by miR-126-overexpression-induced downregulation of LIN28A, although the level of LIN28A protein was much lower in the siLIN28A-transfected cells. These results indicate that miR-126 suppresses JEG-3 cell invasion by targeting LIN28A, and suggest that miR-126-mediated downregulation of LIN28A might contribute to the onset/deterioration of preeclampsia.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • PDE5阻害剤は妊娠高血圧症の治療薬となるか

    西村友宏.

    ファルマシア (日本薬学会)  56 ( 8 ) 785 - 785 2020.08

    Article, review, commentary, editorial, etc. (scientific journal), Single Work,  ISSN  0014-8601

    　View Summary

    妊娠高血圧症は妊娠中に発症する高血圧の総称で妊婦の5～8％に発症することが知られる．中でも妊娠高血圧腎症は，タンパク尿，臓器不全，胎盤機能不全を伴うことが知られ(ただし，2018年のガイドライン改定によりタンパク尿は診断要件から外れた)，特に重篤である．
    なお，本稿は下記の文献に基づいて，その研究成果を紹介するものである.
    1) Herraiz S. et al., BJOG., 119, 1394-1402(2012)．2) Yoshikawa K. et al., Am. J. Hypertens, 31, 89-96(2017)．
    3) Maki S. et al., J. Clin. Med., 8, 856(2019)．
    4) Hawkes N., BMJ., 362, k3247(2018)．
    5) Furuhashi F. et al., J. Matern Fetal Neonatal Med., 17, 1-7(2019)．
    6) Walton R. B. et al., Hypertension, 72, 167-176(2018)．

  • 妊娠による生理学的変化と薬物動態

    西村友宏, 野口幸希.

    薬事 (㈱じほう)  62 ( 4 ) 33 - 44 2020.03

    ISSN  0016-5980

  • Committee for Academic Affairs JSSHP Research Award 2019 Basic Research Screening of an Angiotensin II Receptor Blocker with Low Adverse Fetal Effect using Adverse Event Reporting System and Mechanism of the Low Placental Transfer

    Nishimura Tomohiro, Ishikawa Yu, Noguchi Saki, Tomi Masatoshi

    Hypertension Research in Pregnancy (日本妊娠高血圧学会)  8 ( 1 ) 3 - 3 2020

    ISSN  2187-5987

  • 胎児成長における胎盤ビタミンCトランスポーターの重要性

    西村友宏.

    ファルマシア (日本薬学会)  47 ( 3 ) 249 - 250 2017.03

    Article, review, commentary, editorial, etc. (scientific journal), Single Work,  ISSN  0014-8601

  • How the brain acts: Factor analysis of placebo effects

    ISAWA Minae, SHINNO Akemi, NISHIMURA Tomohiro, TOMI Masatoshi, NAKASHIMA Emi

    JOURNAL OF JAPANESE COSMETIC SCIENCE SOCIETY (Japanese Cosmetic Science Society)  37 ( 3 ) 197 - 200 2013.09

    Research paper, summary (national, other academic conference), Joint Work,  ISSN  1880-2532

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Presentations 【 Display / hide 】

  • ヒト血管内皮細胞HUEhT-1による絨毛外栄養膜細胞HTR-8/SVneoの浸潤誘導

    田島幸佳, 西村友宏, 野口幸希, 登美⻫俊

    日本薬学会第143年会 (札幌) , 

    2023.03
    , 

    Poster presentation

  • 近位尿細管有機アニオントランスポーターを介したメチルマロン酸の輸送の評価

    小林咲央里, 野口幸希, 中田柚貴子,西村友宏, 登美斉俊

    日本薬学会第143年会 (札幌) , 

    2023.03
    , 

    Poster presentation

  • 胎盤における有機カチオン輸送体発現量種差の解析

    山内青依, 中口佳美　野口幸希, 西村友宏, 登美斉俊

    日本薬学会第143年会 (札幌) , 

    2023.03
    , 

    Poster presentation

  • 単一細胞遺伝子発現解析に基づくマウス栄養膜幹細胞から分化する細胞集団の分布

    石鍋巧朗, 野口幸希, 菅沼名津季, 西村友宏, 登美斉俊

    第30回日本胎盤学会学術集会 (金沢) , 

    2022.11
    , 

    Oral presentation (general)

  • JEG-3細胞におけるpropionic acid輸送機構

    粕谷朱里, 野口幸希, 西村友宏, 登美斉俊

    第30回日本胎盤学会学術集会 (金沢) , 

    2022.11
    , 

    Oral presentation (general)

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

  • 子宮内膜螺旋動脈の成熟過程依存的な妊娠高血圧症候群に対する薬物療法の開発

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(C), Principal investigator

  • 降圧薬同効薬間の有害事象報告頻度比較分析に基づく妊娠高血圧症治療薬開拓

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • Adverse fetal effect of thalidomide via semen

    2016.04
    -
    2017.03

    日本医療研究開発機構（AMED）, Research on Regulatory Science of Pharmaceuticals and Medical Devices, Principal investigator

  • Functional expression of sensing foctors against maternal osmotic stress in the placenta

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • エズリンを基軸とする胎児発育制御分子ネットワーク

    2014.04
    -
    2015.03

    上原記念生命科学財団, No Setting

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Awards 【 Display / hide 】

  • TOP REVIEWER 2020

    2020, J Pharm Sci

    Type of Award： Honored in official journal of a scientific society, scientific journal

  • 学術奨励賞（基礎部門）

    2019, 日本妊娠高血圧学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 奨励賞

    2019, 日本薬剤学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • TOP REVIEWER 2019

    2019, J Pharm Sci

    Type of Award： Honored in official journal of a scientific society, scientific journal

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Courses Taught 【 Display / hide 】

  • BIOPHARMACEUTICS

    2021, Autumn Semester, Lecture, Outside own faculty (within Keio)

  • PHARMACOKINETICS

    2021, Lecture, Outside own faculty (within Keio)

  • APPLIED PHARMACOKINETICS

    2019, Spring Semester, Lecture, Within own ｆaculty

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2023

  • ENGLISH EXERCISES FOR PHARMACEUTICAL SCIENCES

    2023

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