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

  • 「ニガテさん」のための薬物動態

    榎木裕紀, 松元一明, じほう, 2021.07,  Page: 230

    Scope: 第4章 患者背景によるADMEの変化に注目できる!ー高齢者の薬物動態ー,  Contact page: 154-161

  • スペシャル・ポピュレーションの抗菌薬投与設計

    榎木裕紀, 松元一明, じほう, 2020.07,  Page: 226

    Scope: 8.四肢切断患者,  Contact page: 212-219

  • Molecular mechanism of muscle wasting in CKD

    Watanabe H, Enoki Y, Maruyama T, Recent Advances of Sarcopenia and Frailty in CKD, 2020.01

     View Summary

    © Springer Nature Singapore Pte Ltd. 2020. Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and a decreased muscle endurance. Many insights have made into the molecular mechanisms of muscle atrophy in CKD. A persistent imbalance between protein synthesis and degradation causes a loss of muscle mass. A decrease in insulin/IGF-1-Akt-mTOR signaling and an increased ubiquitin-proteasome system (UPS) have emerged as inducers of muscle loss. During muscle wasting, abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in skeletal muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The binding of myostatin to its receptor ActRIIB stimulates the expression of Foxo-dependent atrogenes. An impaired mitochondrial function also contributes to reduced muscle endurance. Increased glucocorticoid, angiotensin II, parathyroid hormone, and protein-bound uremic toxin levels that are observed in CKD all have a negative effect on muscle mass and endurance. The loss of skeletal muscle mass during the progression of CKD further contributes to the development of renal failure. Some potential therapeutic approaches based on the molecular mechanisms of muscle wasting in CKD are currently in the testing stages using animal models and clinical settings.

  • 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

  • Impact of rifampicin on the pharmacokinetics of clarithromycin and 14-hydroxy clarithromycin in patients with multidrug combination therapy for pulmonary Mycobacterium avium complex infection.

    Iketani O, Komeya A, Enoki Y, Taguchi K, Uno S, Uwamino Y, Matsumoto K, Kizu J, Hasegawa N

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy  2021.10

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

  • Advanced oxidation protein products contribute to chronic kidney disease-induced muscle atrophy by inducing oxidative stress via CD36/NADPH oxidase pathway.

    Kato H, Watanabe H, Imafuku T, Arimura N, Fujita I, Noguchi I, Tanaka S, Nakano T, Tokumaru K, Enoki Y, Maeda H, Hino S, Tanaka M, Matsushita K, Fukagawa M, Maruyama T

    Journal of cachexia, sarcopenia and muscle  2021.10

    Research paper (scientific journal), Accepted,  ISSN  2190-5991

  • Asymmetric Total Syntheses of Both Enantiomers of Plymuthipyranone B and Its Unnatural Analogues: Evaluation of <i>anti</i>-MRSA Activity and Its Chiral Discrimination.

    Moriyama M, Liu X, Enoki Y, Matsumoto K, Tanabe Y

    Pharmaceuticals (Basel, Switzerland) 14 ( 9 )  2021.09

    Research paper (scientific journal), Accepted

  • Different intra-cerebrospinal distribution of linezolid in patients with inflammatory meningitis.

    Ichinose N, Yoshikawa G, Fukao E, Ichisawa M, Takahata T, Enoki Y, Taguchi K, Oda T, Tsutsumi K, Matsumoto K

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (International Journal of Infectious Diseases)  110   382 - 384 2021.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1201-9712

     View Summary

    Linezolid has excellent antibiotic activity against gram-positive organisms and is expected to be an alternative to vancomycin for the treatment of bacterial meningitis. Accumulated evidence has shown the superior pharmacokinetic characteristics of linezolid to vancomycin, such as cerebrospinal fluid penetration. However, in the treatment of meningitis, pharmacokinetic information regarding the intra-cerebrospinal distribution of linezolid and the effects of drainage on the linezolid concentration in the cerebrospinal fluid are unclear. This report describes two patient cases, in which the linezolid concentrations in the cerebrospinal fluid were in the following order: subarachnoid space (cisternal drainage and lumbar puncture) ≥ third ventricle > lateral ventricle. In addition, the linezolid concentration in the cerebrospinal fluid, collected via lumbar puncture, tended to increase after removal of the drainage. This report is novel in presenting two cases of meningitis that showed different intra-cerebrospinal distribution of linezolid in various parts of the central nervous system and an increased linezolid concentration in the cerebrospinal fluid after removal of the drainage.

  • Augmented clearance of nivolumab is associated with renal functions in chronic renal disease model rats.

    Taguchi K, Hayashi Y, Ohuchi M, Yamada H, Yagishita S, Enoki Y, Matsumoto K, Hamada A

    Drug metabolism and disposition: the biological fate of chemicals  2021.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0090-9556

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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

     View Summary

    <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

     View Summary

    <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

  • 【難しい数式も、TDMもわからない!「ニガテさん」のための薬物動態】(第4章)患者背景によるADMEの変化に注目できる! 高齢者の薬物動態

    榎木 裕紀, 松元 一明

    調剤と情報, 2021.07, (株)じほう

  • ヘモグロビンを担体とした一酸化炭素製剤の閉塞性細気管支炎に対する治療効果の解析

    渡部 佑樹, 田口 和明, 榎木 裕紀, 酒井 宏水, 丸山 徹, 小田切 優樹, 河野 光智, 松元 一明

    日本DDS学会学術集会プログラム予稿集, 2021.06, Other, 日本DDS学会

  • Clostridioides difficile感染症治療薬のin vitro抗菌活性及びマウス糞中濃度評価

    田代 渉, 水上 雄貴, 榎木 裕紀, 田口 和明, 松元 一明

    日本化学療法学会雑誌, 2021.04, Other, (公社)日本化学療法学会

  • COVID-19に対するレムデシビルの有効性と安全性に関するメタ解析

    本間 杏花, 榎木 裕紀, 五十嵐 裕貴, 渡部 佑樹, 鈴木 悠斗, 林 侑孝, 平岡 奏, 田口 和明, 松元 一明

    日本薬学会年会要旨集, 2021.03, Other, (公社)日本薬学会

  • テジゾリドとリネゾリドの有効性、安全性に関するメタアナリシス

    宍戸 詩乃, 田代 渉, 三澤 可奈, 竹村 渉, 佐伯 怜香, 榎木 裕紀, 田口 和明, 松元 一明

    日本薬学会年会要旨集, 2021.03, Other, (公社)日本薬学会

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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

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2021

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2021

  • ENGLISH EXERCISES FOR PHARMACEUTICAL SCIENCES

    2021

  • DRUG INFORMATION AND PHARMACODYNAMICS

    2021

  • BACHELOR'S THESIS

    2021

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