Enoki, Yuki



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


Assistant Professor/Senior Assistant Professor


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

  • Fecal pharmacokinetics/pharmacodynamics characteristics of fidaxomicin and vancomycin against Clostridioides difficile infection elucidated by in vivo feces-based infectious evaluation models.

    Tashiro S, Taguchi K, Enoki Y, Matsumoto K

    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases  2022.12

    ISSN  1198-743X

  • The G protein-coupled receptor ligand apelin-13 ameliorates skeletal muscle atrophy induced by chronic kidney disease.

    Enoki Y, Nagai T, Hamamura Y, Osa S, Nakamura H, Taguchi K, Watanabe H, Maruyama T, Matsumoto K

    Journal of cachexia, sarcopenia and muscle  2022.12

    ISSN  2190-5991

  • Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system

    Ozawa T., Namkoong H., Takaya R., Takahashi Y., Fukunaga K., Enoki Y., Taguchi K., Kizu J., Matsumoto K., Hasegawa N.

    BMC Infectious Diseases (BMC Infectious Diseases)  22 ( 1 ) 580 2022.12

     View Summary

    Background: In Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database. Methods: We included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution. Results: The total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181–300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3–7.44), 2.61 (95% CI, 1.39–4.91), and 2.38 (95% CI, 1.04–5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62–351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35–14.77) and 6.99 (95% CI, 3.22–15.18). The β value of EB was 2.07 (95% CI, 1.48–2.76), which was classified as a wear-out failure type. Conclusions: For MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.

  • Safety of linezolid in patients with decreased renal function and trough monitoring: a systematic review and meta-analysis.

    Liu X, Aoki M, Osa S, Ito C, Saiki R, Nagai T, Enoki Y, Taguchi K, Matsumoto K

    BMC pharmacology & toxicology 23 ( 1 ) 89 2022.11

  • Sciatic denervation-induced skeletal muscle atrophy is associated with persistent inflammation and increased mortality during sepsis.

    Osa S, Enoki Y, Miyajima T, Akiyama M, Fujiwara Y, Taguchi K, Kim YG, Matsumoto K

    Shock (Augusta, Ga.)  2022.11

    ISSN  1073-2322

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

Reviews, Commentaries, etc. 【 Display / hide

  • Evaluation of <i>in vitro</i> antibacterial activities of therapeutic drugs against <i>Clostridioides difficile</i>, and measurement of fecal concentrations in <i>Clostridioides difficile</i> infection mouse models.

    Tashiro Sho, Mizukami Yuki, Enoki Yuki, Taguchi Kazuaki, Matsumoto Kazuaki

    Proceedings for Annual Meeting of The Japanese Pharmacological Society (Japanese Pharmacological Society)  95 ( 0 ) 1-YIA-30 2022

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    <p><b>[Background, Purpose]</b> Metronidazole (MNZ), vancomycin (VCM), and fidaxomicin (FDX) are standard therapeutic drugs against <i>Clostridioides difficile</i> infection (CDI). MNZ resulted in lower clinical cure rate compared with VCM. Detail information about antibacterial activities of the drugs and reasons for MNZ inferiority are not clear. Therefore, we evaluated the <i>in vitro</i> antibacterial activities, and measured fecal concentrations in CDI mouse models. </p><p><b>[Method] </b>Minimum inhibitory concentration (MIC) against seven strains of <i>C. difficile</i> were determined. Time-kill curves and post-antibiotic effect (PAE) were determined against <i>C. difficile</i> ATCC<sup>®</sup>43255. In addition, fecal concentrations in CDI mouse models were measured. </p><p><b>[Results] </b>MNZ, VCM, and FDX geometric mean MIC were 0.91, 1.81, and 0.34 µg/mL, respectively. MNZ exhibited concentration-dependent and rapid antibacterial activities at low concentrations ranged from 0.5 to 2.0 µg/mL. On the other hands, VCM and FDX exhibited time-dependent and slow antibacterial activities at high concentrations ranged from 0.5 to 32 µg/mL.<b> </b>MNZ showed the shortest PAE (1.9 h).<b> </b>In addition, maximal fecal concentration of MNZ (21.7 µg/g) was significantly lower than that of VCM (222.7 µg/g) at the dose of 40 mg/kg. </p><p><b>[Conclusion] </b>MNZ exhibited noteworthy antibacterial activities against <i>C. difficile</i>. However, MNZ PAE was short, and the fecal exposure was significantly small. We think the two characteristics are responsibility for the MNZ inferiority in clinical cure rate.</p>

  • 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, 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, 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 ) 298 2013

    Other, Joint Work

Presentations 【 Display / hide

  • 一酸化炭素を基盤とした急性呼吸窮迫症候群に対する新規治療法の検討

    渡部 佑樹, 田口 和明, 榎木 裕紀, 小田切 優樹, 酒井 宏水, 松元 一明




  • メトヘモグロビン-アルブミンクラスターの硫化水素中毒解毒剤としての有用性評価

    鈴木 悠斗, 田口 和明, 岡本 航, 榎木 裕紀, 小松 晃之, 松元 一明




  • ドキソルビシン担持一酸化炭素結合型ヘモグロビン-アルブミンクラスターの創製と抗腫瘍効果の評価

    伊藤 千尋, 田口 和明, 山田 大雅, 榎木 裕紀, 小松 晃之, 松元 一明




  • エクソソームによる廃用性筋萎縮における敗血症予後増悪

    長 邑花, 榎木 裕紀, 松元 一明, 田口 和明




  • 慢性腎臓病誘発サルコペニアにおける尿毒症物質の関与とapelinの有用性評価

    榎木 裕紀, 永井 智也, 濱村 有那, 長 邑花, 渡邊 博志, 丸山 徹, 田口 和明, 松元 一明




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

  • 骨格筋由来エクソソームによるサルコペニア合併敗血症増悪機序の解明


    Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, No Setting

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  • Strategy for the treatment of CKD-induced sarcopenia based on the crosstalk between myokine and uremic toxins


    MEXT,JSPS, Grant-in-Aid for Scientific Research, ENOKI YUKI, Grant-in-Aid for Early-Career Scientists , Principal investigator

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    In a mouse model of chronic kidney disease (CKD), the skeletal muscle weight and the cross-sectional area of the muscle fiber appeared to gradually decrease after the CKD surgery; expression of apelin-a skeletal muscle-derived secretory factor also decreased in the skeletal muscles. The administration of charcoal, a uremic toxin adsorbent, suppressed the decrease in apelin and skeletal muscle mass. Furthermore, apelin suppressed the decrease in skeletal muscle mass in CKD mice. The findings suggest that uremic toxin-mediated downregulation of apelin may play an important role in the pathophysiology of CKD-induced sarcopenia. Apelin, therefore could be a promising therapeutic target for CKD-induced sarcopenia.

Awards 【 Display / hide

  • 第13回日本化学療法学会東日本支部 支部長賞(臨床)

    劉小茜、長邑花、榎木裕紀、田口和明、松元一明, 2022.01, 日本化学療法学会東日本支部, リネゾリドによる血液毒性に与える腎障害またはトラフ値の影響

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

  • 第13回日本化学療法学会東日本支部 支部奨励賞(基礎)

    三澤可奈、西村知泰、榎木裕紀、田口和明、宇野俊介、上蓑義典、松元一明、長谷川直樹, 2022.01, 日本化学療法学会東日本支部, Mycobacterium abscessus complexに対するNacubactamとβラクタム薬の併用効果

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

  • 第31回日本医療薬学会年会 Young Investigator’s Award

    長邑花、榎木裕紀、田口和明、松元一明, 2021.10, 日本医療薬学会, 廃用性筋萎縮による敗血症病態増悪における骨格筋由来エクソソームの関与

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

  • 第28回日本血液代替物学会年次大会優秀発表賞

    渡部佑樹、田口和明、榎木裕紀、酒井宏水、小田切優樹、松元一明, 2021.10, 日本血液代替物学会, 一酸化炭素結合型ヘモグロビン小胞体の急性呼吸窮迫症候群に対する有用性評価

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

  • MRSAフォーラム2020 一般演題優秀賞

    田代渉、北廣夕貴、森山大夢、濱村有那、高畑勇、川邊理奈、榎木裕紀、田口和明、松元一明, 2021.07, MRSAフォーラム, MRSA菌血症に対するダプトマイシンとバンコマイシンの有効性及び安全性の評価:システマティックレビュー&メタ解析

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

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Courses Taught 【 Display / hide











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