Enoki, Yuki

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 薬効解析学講座 (Shiba-Kyoritsu)

Position

Research Associate/Assistant Professor/Instructor

 

Books 【 Display / hide

  • 調剤と情報-高齢者の低栄養と薬-

    ENOKI YukiMATSUMOTO Kazuaki, JIHO, 2018.10

    Scope: 高齢者が低栄養になるとどうなる?-体内動態の変化と服薬上のリスク-

  • 新薬展望2018

    Matsumoto KazuakiENOKI Yuki, Medicine and Drug Journal, 2018.02

    Scope: 抗菌薬

Papers 【 Display / hide

  • The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing.

    Tsutsuura M, Moriyama H, Kojima N, Mizukami Y, Tashiro S, Osa S, Enoki Y, Taguchi K, Oda K, Fujii S, Takahashi Y, Hamada Y, Kimura T, Takesue Y, Matsumoto K

    BMC infectious diseases (BMC Infectious Diseases)  21 ( 1 ) 153 2021.02

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Background: This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. Methods: We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results: Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47–0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15–20 μg/mL (OR 2.39, 95% CI 1.78–3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18–0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13–3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28–1.01); however, it was not significant in the analysis of mortality. Conclusions: We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

  • The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses.

    Moriyama H, Tsutsuura M, Kojima N, Mizukami Y, Tashiro S, Osa S, Enoki Y, Taguchi K, Oda K, Fujii S, Takahashi Y, Hamada Y, Kimura T, Takesue Y, Matsumoto K

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (Journal of Infection and Chemotherapy)  27 ( 5 ) 781 - 785 2021.02

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1341-321X

     View Summary

    We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity in pediatric patients. We conducted our analysis using MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials as electronic databases (June 29, 2019). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 16 studies that were eligible for the meta-analysis. A total of 351 and 3,266 patients were included in the analysis for effectiveness and nephrotoxicity, respectively. Pediatric MRSA infection patients with VCM trough concentrations ≥ 10 μg/mL had significantly lower treatment failure rates (OR 0.54, 95% CI 0.30–0.96). The incidence of nephrotoxicity was significantly higher in trough concentrations ≥ 15 μg/mL than when they were < 15 μg/mL (OR 3.02, 95% CI 2.08–4.38). We identified the optimal VCM trough concentrations associated with effectiveness and nephrotoxicity in pediatric patients with MRSA infection. Further prospective studies are needed to find optimal dosing and monitoring strategy on VCM in pediatric population.

  • Pharmacokinetics/Pharmacodynamics Evaluation of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli In Vitro and In Vivo in a Murine Thigh Infection Model.

    Tashiro S, Hayashi M, Takemura W, Igarashi Y, Liu X, Mizukami Y, Kojima N, Enoki Y, Taguchi K, Yokoyama Y, Nakamura T, Matsumoto K

    Pharmaceutical research (Pharmaceutical Research)  38 ( 1 ) 27 - 35 2021.01

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

     View Summary

    Purpose: Although flomoxef (FMOX) has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of FMOX against ESBL-producing E. coli is unclear. The aim of this study was to determine the PK/PD index of FMOX against ESBL-producing E. coli. Methods: In vitro time-kill curve studies and in vivo PK/PD experiments were carried out. Results: Time–kill curves exhibited a unique bactericidal activity: time-dependent activity at low concentrations and concentration-dependent activity at high concentrations. In neutropenic murine thigh infection experiments, the antibacterial activity of FMOX correlated with the time that the free drug concentration remaining above the minimum inhibitory concentration (MIC) (fT>MIC) and the ratio of the area under the free drug concentration–time curve for a 24 h period to the MIC (fAUC /MIC). However, the burden of ESBL producing E. coli significantly reduced when the time intervals for administration were shorter among three dosage regimens with same magnitude of fAUC /MIC, indicating that fT>MIC is significant PK/PD index. The target value of fT>MIC for 1 log kill reduction was 35.1%. Conclusions: fT>MIC is the most significant PK/PD index of FMOX against ESBL-producing E. coli and its target value is ≥ 40%. 24 24 10

  • Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses.

    Kuroda T, Minamijima Y, Niwa H, Tamura N, Mita H, Fukuda K, Kaimachi M, Suzuki Y, Enoki Y, Taguchi K, Matsumoto K, Toutain PL, Bousquet-Melou A, Kasashima Y

    Equine veterinary journal (Equine Veterinary Journal)   2020.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0425-1644

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    Background: First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. Objective: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. Study design: Experimental study with single administration. Methods: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC-MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method. Results: The percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h. Main limitations: Small sample size only in healthy horses. Conclusions: For CET, more frequent administration than that currently recommended (22 mg/kg bwt q6–12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen currently proposed (10–22 mg/kg bwt q6h) could control S. zooepidemicus and S. aureus infections in horses. 90 90

  • Remdesivir for the treatment of coronavirus COVID-19: A meta-analysis of randomised controlled trials.

    Enoki Y, Igarashi Y, Watabe Y, Honma K, Suzuki Y, Hayashi Y, Hiraoka K, Taguchi K, Matsumoto K

    Journal of global antimicrobial resistance (Journal of Global Antimicrobial Resistance)  24   81 - 82 2020.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2213-7165

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Reviews, Commentaries, etc. 【 Display / hide

  • A post-transplantation patient in whom a specific interval was required until the blood concentration of fluconazole reached a steady state

    Sakamoto Yasutaka, Matsumoto Kazuaki, Isono Hikaru, Koike Hirofumi, Enoki Yuki, Taguchi Kazuaki, Hagihara Maki, Matsumoto Kenji, Nakajima Hideaki, Sahashi Yukiko

    Proceedings for Annual Meeting of The Japanese Pharmacological Society (Japanese Pharmacological Society)  93 ( 0 ) 2 - O-036 2020

    Other article, Joint Work

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    <p>[Introduction]</p><p>Fluconazole is anti-fungal agent widely used to prophylaxis and treatment. In the ECIL6 Guidelines, it is recommended that the dose of FLCZ for treatment should be established as ≥10 to 15 mg/mL, which is a trough level. We report a patient in whom a specific interval was required until the blood concentration of FLCZ reached a steady state.</p><p>[Case]</p><p>The patient was a 50-year-old male. To treat acute lymphocytic leukemia, remission induction and consolidation therapies were performed. After remission was achieved, umbilical cord blood transplantation was conducted. On Day 18, graft survival was confirmed. A blood culture test on Day 27 detected yeast-like fungus. Micafungin (MCFG) at 150 mg, used for empiric therapy, was switched to liposomal amphotericin B (L-AMB) at 3 mg/kg. On Day 36, renal hypofunction was noted, and L-AMB was switched to MCFG at 150 mg. On Day 65, there was a decrease in the β-D-glucan level from ≥600 to 375.2 pg/mL, and MCFG at 150 mg was switched to FLCZ at 200 mg. On Day 71, the trough level of FLCZ was 21.0 mg/mL, and its concentration 2 hours after administration was 24.4 mg/mL. The β-D-glucan level was 232.1 pg/mL. On Day 79, the trough and 2-hour levels of FLCZ were 30.6 and 32.1 mg/mL, respectively, and the β-D-glucan level was 167.6 pg/mL. On Day 85, the trough level of FLCZ was 38.4 mg/mL, and the β-D-glucan level was 161.4 pg/mL. Subsequently, blood culture was negative, and FLCZ administration was continued until Day 229. During the administration period, the creatinine clearance ranged from 33.0 to 45.9 mL/min.</p><p>[Discussion]</p><p>The half-life of FLCZ is approximately 30 hours. Its clearance depends on the renal function. In the present case, a target trough level was achieved in the early phase, but the blood concentration of FLCZ increased with the prolongation of the administration period. Therefore, the appearance of central nervous toxicity must be considered. In the future, it may be necessary to establish individualized, optimized FLCZ dosimetry in accordance with the renal function for the optimal use of FLCZ.</p>

  • Factorial Analysis of Clostridioides Difficile Colitis and Pseudomembranous Colitis Using JADER

    Takaya Risako, Misawa Kana, Tashiro Sho, Enoki Yuki, Taguchi Kazuaki, Matsumoto Kazuaki

    BPB Reports (公益社団法人 日本薬学会)  3 ( 1 ) 1 - 6 2020

    Other article, Joint Work

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    <p>Clostridioides difficile (C. difficile) colitis and pseudomembranous colitis are known as healthcare-associated intestinal infections. In this study, the incidence of C. difficile colitis and pseudomembranous colitis was investigated using the Japanese Adverse Drug Event Report (JADER). Using JADER data between April 2004 and September 2017, the patient who developed C. difficile colitis and pseudomembranous colitis were investigated. During the study period, 375 cases of C. difficile colitis and 903 cases of pseudomembranous colitis were reported. The numbers of reported cases of both C. difficile colitis and pseudomembranous colitis were largest in those in their 70s, accounting for 24.7% and 25.6%, respectively. Patients in their 60s-90s comprised the majority of all patients with both C. difficile colitis and pseudomembranous colitis. Both C. difficile colitis and pseudomembranous colitis were caused by antibiotics in many patients, and signals of all antibiotics were detected. In C. difficile colitis, signals of immunosuppressants, corticosteroids, and alkylating drugs were also detected among drugs other than antibiotics. For pseudomembranous colitis, the use of molecularly targeted drugs, antimetabolic drugs, and corticosteroids was reported other than antibiotics. Using JADER, we revealed risk factors for the development of C. difficile colitis and pseudomembranous colitis, and firstly revealed that molecularly targeted drugs other than antibiotics could also be potential risk factors. Our findings may be useful for the early detection of drug-induced C. difficile colitis and pseudomembranous colitis.</p>

  • 土-P2-280 異常ファーマコキネティクスを示したフェニトイン投与患者における要因解析(TDM・投与設計,ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来)

    平田 憲史郎, 猿渡 淳二, 渡邊 博志, 丸山 徹, 福永 栄子, 岩田 一史, 浦田 由紀乃, 四郎園 巧, 上田 賢太郎, 合澤 啓二, 陣上 祥子, 榎木 裕紀, 前田 仁志

    The Annual Meeting of Japanese Society of Pharmaceutical Health Care and Sciences (Japanese Society of Pharmaceutical Health Care and Sciences)  23 ( 0 )  2013

    Other article, Joint Work

Presentations 【 Display / hide

  • 腎機能障害を伴う高齢者におけるダプトマイシンのクリアランスと各種腎機能評価法に関する検討

    佐村 優, 高田 啓介, 山本 理紗子, 伊藤 勇人, 南雲 史雄, 内田 仁樹, 倉田 武徳, 腰岡 桜, 榎木 裕紀, 田口 和明, 谷川 浩司, 松元 一明

    日本腎臓病薬物療法学会誌, 2020.11, Other, 日本腎臓病薬物療法学会

  • Clostridioides difficile感染症に対するメトロニダゾールとバンコマイシンの有効性及び安全性評価

    三澤 可奈, 池谷 修, 榎木 裕紀, 田口 和明, 松元 一明, 宇野 俊介, 上蓑 義典, 長谷川 直樹

    日本化学療法学会雑誌, 2020.09, Other, (公社)日本化学療法学会

  • 非好中球減少患者のカンジダ血症におけるアゾール系薬とポリエン系薬の有効性及び安全性に関するsystematic review、メタ解析

    長 邑花, 田代 渉, 五十嵐 裕貴, 劉 小茜, 榎木 裕紀, 田口 和明, 真弓 俊彦, 竹末 芳生, 松元 一明, 渡部 佑樹

    日本化学療法学会雑誌, 2020.09, Other, (公社)日本化学療法学会

  • 造血器腫瘍患者及びそれ以外の患者におけるcandida血症の原因菌と薬剤感受性比較

    坂本 靖宜, 鈴木 智代, 川邊 一寛, 榎木 裕紀, 田口 和明, 加藤 英明, 松元 一明, 小池 博文, 佐橋 幸子

    日本化学療法学会雑誌, 2020.09, Other, (公社)日本化学療法学会

  • 造血器腫瘍患者におけるフルコナゾールの母集団薬物動態解析

    坂本 靖宜, 磯野 ひかる, 榎木 裕紀, 田口 和明, 松元 一明, 萩原 真紀, 松本 憲二, 小池 博文, 中島 秀明, 佐橋 幸子

    日本化学療法学会雑誌, 2020.09, Other, (公社)日本化学療法学会

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

  • 筋作動因子-尿毒症物質クロストークを標的としたCKD誘発サルコペニアの治療戦略

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 榎木 裕紀, Grant-in-Aid for Early-Career Scientists , Principal Investigator

     View Summary

    本研究は、慢性腎臓病誘発サルコペニアにおける筋作動因子および尿毒症物質のプロファイルによる病態構造を基盤としたサルコペニアの予防・診断ならびに新規治療戦略を構築するための基盤的情報を明らかにすることである。そのため、本年は、慢性腎臓病誘発サルコペニアモデルマウスを用いて、骨格筋萎縮病態形成の経過について検討し、それに伴う筋作動因子の変動について検討した。慢性腎臓病モデル作製後、4、8、12週と経過するに伴い、体重、腓腹筋、前脛骨筋、ヒラメ筋の重量が減少した。また骨格筋萎縮関連遺伝子である、atrogin-1遺伝子発現は増加し、骨格筋断面積も減少した。顕著な差は12週から認められたものの、8週目においても上述した筋萎縮関連因子の変動が認められた。また骨格筋ミトコンドリア活性を指標としたコハク酸デヒドロゲナーゼ染色による筋線維タイプの検討において、モデルの経過に従い、ミトコンドリア活性の低下が観察された。慢性腎臓病によって持続的にサルコペニア病態が誘導されていることを確認した。そこで骨格筋における各種筋作動因子の発現について評価した。骨格筋の萎縮や筋タンパク分解との関与が報告されているmyostatinは、経月的に増加していた。しかし炎症因子であるmif発現に変動は認められなかった。一方、骨格筋肥大との関連が報告されている筋作動因子であるirisinについては8週目において一過性の上昇が観察されたものの、12週においては減少していた。また筋肥大作用を有する成長因子であるigf-1に変化はみられなかった。
    慢性腎臓病誘発サルコペニアモデルの作製に成功し、それに伴う筋作動因子の発現について検討できている。すでに尿毒症物質を吸着する活性吸着炭(AST-120)を用いた検討を進めており、今後経過について評価する予定である。以上のことから概ね順調に進展している。
    今後は、現在進行中である慢性腎臓病誘発サルコペニアモデルに対するAST-120投与による筋作動因子への影響について評価を行う。また2次性副甲状腺機能亢進症(SHPT)モデルの作製とSHPT治療薬の筋作動因子の発現に及ぼす影響について検討を進める。In vitro培養細胞を用いた検討により尿毒症物質が筋作動因子発現に及ぼす影響とその発現機序について検討を進める。

Awards 【 Display / hide

  • 真菌症フォーラム2020奨励賞

    榎木裕紀他, 2020.12, 日本医真菌学会, カンジダ血症におけるカテーテル抜去の有用性に関する検討:ランダム化比較 試験のサブグループ解析に基づく検証

    Type of Award: Awards of National Conference, Council and Symposium.  Country: 日本

 

Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD (PHARMACODYNAMICS)

    2021

  • SEMINAR (PHARMACODYNAMICS)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PRIOR LEARNING FOR CLINICAL PRACTICE 4

    2021

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2021

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