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Papers - Enoki, Yuki

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日々の感染症診療コンサルテーション:興味ある症例との遭遇血中濃度測定によりダプトマイシンの投与が完遂できた1例

一ノ瀬直樹, 小田智三, 山本理紗子, 高野哲史, 宇佐見まみ, 大場邦弘, 榎木裕紀, 田口和明, 松元一明

日本化学療法学会雑誌 ((公社)日本化学療法学会) 68 ( Suppl.A ) 238 - 238 2020.09

ISSN 1340-7007

Azoles versus conventional amphotericin B for the treatment of candidemia: A meta-analysis of randomized controlled trials.

Osa S, Tashiro S, Igarashi Y, Watabe Y, Liu X, Enoki Y, Taguchi K, Mayumi T, Miyazaki Y, Takesue Y, Matsumoto K

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (Journal of Infection and Chemotherapy) 26 ( 11 ) 1232 - 1236 2020.08

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

© 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Because exclusive use of echinocandins can induce the drug-resistant strains, appropriate use of azoles and polyenes is still necessary in the treatment of candidemia. In this study, we conducted a meta-analysis of randomized controlled trials regarding the efficacy and safety of azole and polyene antifungals in the treatment of candidemia. MEDLINE and the Cochrane Register of Controlled Trials were used as reference databases, and papers published up to June 10, 2019 were searched. The search results were carefully scrutinized, duplicate references were removed, and the study was ultimately carried out using three reports. Among azole antifungals, fluconazole and voriconazole were extracted, however; only conventional amphotericin B (AMPH-B) was extracted among polyene antifungals. Treatment successes with the use of azoles and AMPH-B were compared, and findings showed that AMPH-B was significantly superior (RR = 0.90, 95% CI 0.82–1.00, p = 0.04). However, there was no significant difference in mortality (RR = 0.87, 95% CI 0.72–1.07, p = 0.19). Analysis of adverse events showed that renal disorders were significantly less common with azoles than with AMPH-B (RR = 0.26, 95% CI 0.10–0.68, p = 0.006). In conclusion, AMPH-B were superior to azoles in terms of efficacy, but had a risk of causing renal disorders.

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Indoxyl Sulfate Contributes to Adipose Tissue Inflammation through the Activation of NADPH Oxidase.

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

Toxins (Toxins) 12 ( 8 ) 502 2020.08

Research paper (scientific journal), Joint Work, Accepted

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Adipose tissue inflammation appears to be a risk factor for the progression of chronic kidney disease (CKD), but the effect of CKD on adipose tissue inflammation is poorly understood. The purpose of this study was to clarify the involvement of uremic toxins (indoxyl sulfate (IS), 3-indoleacetic acid, p-cresyl sulfate and kynurenic acid) on CKD-induced adipose tissue inflammation. IS induces monocyte chemoattractant protein-1 (MCP-1) expression and reactive oxygen species (ROS) production in the differentiated 3T3L-1 adipocyte. An organic anion transporter (OAT) inhibitor, an NADPH oxidase inhibitor or an antioxidant suppresses the IS-induced MCP-1 expression and ROS production, suggesting the OAT/NADPH oxidase/ROS pathway is involved in the action of IS. Co-culturing 3T3L-1 adipocytes and mouse macrophage cells showed incubating adipocytes with IS increased macrophage infiltration. An IS-overload in healthy mice increased IS levels, oxidative stress and MCP-1 expression in epididymal adipose tissue compared to unloaded mice. Using 5/6-nephrectomized mice, the administration of AST-120 suppressed oxidative stress and the expression of MCP-1, F4/80 and TNF-α in epididymal adipose tissue. These collective data suggest IS could be a therapeutic target for the CKD-related inflammatory response in adipose tissue, and that AST-120 could be useful for the treatment of IS-induced adipose tissue inflammation.

Concurrent administration with multivalent metal cation preparations or polycationic polymer preparations inhibits the absorption of raltegravir via its chelation.

Enoki Y, Suzuki N, Ito M, Uchiyama E, Kishi N, Ito C, Kitahiro Y, Sakamoto K, Taguchi K, Yokoyama Y, Kizu J, Matsumoto K

The Journal of pharmacy and pharmacology (Journal of Pharmacy and Pharmacology) 72 ( 10 ) 1361 - 1369 2020.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 0022-3573

© 2020 Royal Pharmaceutical Society Objectives: Raltegravir (RAL) that can form chelates with multivalent metal cations shows lateral interactions with multivalent metal cation and polycationic polymer. We investigated the interactions of RAL with multivalent metal cation preparations, Al(OH)3 and LaCO3, and polycationic polymer preparations, bixalomer (Bxl) and sevelamer (Svl). Methods: Immediately before the oral administration of 40 mg/kg RAL, the rats were administered orally with the vehicle, Al(OH)3, LaCO3, Bxl, or Svl, and the time course of RAL serum concentration was followed. The in vitro binding affinity of RAL with multivalent metal cation and polycationic polymer was also evaluated using isothermal titration calorimetry (ITC). Results: When Al(OH)3, LaCO3, Bxl, or Svl was concomitantly administered with RAL, the maximum concentration and area under the curve were significantly lower than those when RAL was administered alone. ITC showed the interaction of RAL with Al(OH)3 as an enthalpy-driven reaction and its interactions with LaCO3 and Bxl as entropy–enthalpy mixed reactions. Conclusions: The interaction of RAL with Al(OH)3, LaCO3, Bxl, or Svl can inhibit RAL absorption into the gastrointestinal tract, and thus, the multivalent metal cation and polycationic polymer are the modifying factors that can affect RAL pharmacokinetics.

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【薬物動態・薬物相互作用・薬物アレルギーから最適化スペシャル・ポピュレーションの抗菌薬投与設計】(第3章)特殊病態の患者四肢切断患者

榎木裕紀, 松元一明

薬事 ((株)じほう) 62 ( 10 ) 2080 - 2087 2020.07

ISSN 0016-5980

＜Key Points＞・四肢切断患者では骨格筋組織の喪失により、血清クレアチニンを指標とした腎機能予測は腎機能を過大評価する恐れがあり不適切である。そのため血清シスタチンCに基づいた腎機能予測が有用である。・血清シスタチンCに基づいた腎機能推算式は、日本腎臓学会の提唱する推定腎糸球体濾過量推算式が日本人患者の腎機能予測に有用である。・四肢切断後の患者において、腎障害は予後不良因子となるため、腎障害を誘発する薬物の投与に当たっては十分な腎機能モニタリングが必要である。・過量投与による腎障害を回避するためには、四肢切断後の実測体重、体表面積補正を用いることが望ましいが、過少投与を避けるための最適な投与方法については今後検証が必要である。(著者抄録)

腎障害患者におけるダプトマイシンの母集団薬物動態解析

伊藤勇人, 佐村優, 山本理紗子, 榎木裕紀, 田口和明, 倉田武徳, 高田啓介, 南雲史雄, 内田仁樹, 松元一明

日本化学療法学会雑誌 ((公社)日本化学療法学会) 68 ( 2 ) 298 - 298 2020.03

ISSN 1340-7007

Clostridioides difficile感染症治療薬の有効性と安全性に関する検討

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 ((公社)日本化学療法学会) 68 ( 2 ) 274 - 274 2020.03

Accepted, ISSN 1340-7007

外来抗菌化学療法を目指した抗菌薬の各種輸液に対する安定性の検討

榎木裕紀, 赤羽根睦実, 佐伯怜香, 林侑孝, 平岡奏, 本間杏花, 板垣万里奈, 後藤田真衣, 篠田こずえ, 羽生聡美, 濱村有那, 宮嶋太智, 田口和明, 池谷修, 宇野俊介, 上蓑義典, 長谷川直樹, 松元一明

日本薬学会年会要旨集 ((公社)日本薬学会) 140年会 26Q - pm002 2020.03

ISSN 0918-9823

Carbon Monoxide Rescues the Developmental Lethality of Experimental Rat Models of Rhabdomyolysis-Induced Acute Kidney Injury.

Kazuaki Taguchi, Shigeru Ogaki, Taisei Nagasaki, Hiroki Yanagisawa, Kento Nishida, Hitoshi Maeda, Yuki Enoki, Kazuaki Matsumoto, Hidehisa Sekijima, Kazuya Ooi, Yu Ishima, Hiroshi Watanabe, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama

The Journal of pharmacology and experimental therapeutics (Journal of Pharmacology and Experimental Therapeutics) 372 ( 3 ) 355 - 365 2020.01

Research paper (scientific journal), Accepted, ISSN 0022-3565

Many victims, after being extricated from a collapsed building as the result of a disaster, suffer from disaster nephrology, a term that is referred to as the crush syndrome (CS). Recommended treatments, which include dialysis or the continuous administration of massive amounts of fluid are not usually easy in cases of such mass natural disasters. In the present study, we examined the therapeutic performance of a biomimetic carbon monoxide (CO) delivery system, CO-enriched red blood cells (CO-RBCs), on experimental animal models of an acute kidney injury (AKI) induced by traumatic and nontraumatic rhabdomyolysis, including CS and rhabdomyolysis with massive hemorrhage shock. A single CO-RBC treatment was found to effectively suppress the pathogenesis of AKI with the mortality in these model rats being improved. In addition, in further studies using glycerol-induced rhabdomyolysis model rats, the pathogenesis of which is similar to that for the CS, AKI and mortality were also reduced as the result of a CO-RBC treatment. Furthermore, CO-RBCs were found to have renoprotective effects via the suppression of subsequent heme protein-associated renal oxidative injury; the oxidation of myoglobin in the kidneys, the generation of reactive oxygen species by free heme produced from degraded-cytochrome P450 and hemoglobin-associated renal injury. Because CO-RBCs can be prepared and used at both hospitals and at a disaster site, these findings suggest that CO-RBCs have the potential for use as a novel cell therapy against both nontraumatic and traumatic rhabdomyolysis including CS-induced AKI. SIGNIFICANCE STATEMENT: After mass natural and man-made disasters, people who are trapped in collapsed buildings are in danger of acute kidney injury (AKI), including crush syndrome (CS)-related AKI. This paper reports that carbon monoxide-enriched red blood cells (CO-RBCs), which can be prepared at both hospitals and disaster sites, dramatically suppressed the pathogenesis of CS-related AKI, thus improving mortality via suppressing heme protein-associated renal injuries. CO-RBCs have the potential for serving as a practical therapeutic agent against disaster nephrology associated with the CS.

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Molecular mechanism of muscle wasting in CKD

Watanabe H, Enoki Y, Maruyama T

Recent Advances of Sarcopenia and Frailty in CKD (Recent Advances of Sarcopenia and Frailty in CKD) 15 - 33 2020.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 9789811523649

© 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.

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Echinocandins versus non-echinocandins for empirical antifungal therapy in patients with hematological disease with febrile neutropenia: A systematic review and meta-analysis

Yamashita C, Takesue Y, Matsumoto K, Ikegame K, Enoki Y, Uchino M, Miyazaki T, Izumikawa K, Takada T, Okinaka K, Ueda T, Miyazaki Y, Mayumi T

Journal of Infection and Chemotherapy (Journal of Infection and Chemotherapy) 26 ( 6 ) 596 - 603 2020

Research paper (scientific journal), Joint Work, Accepted, ISSN 1341321X

© 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on high-quality evidence, most guidelines recommend caspofungin. The aim of this study was to clarify whether echinocandins, including micafungin, are associated with improved clinical outcomes in patients with persistent FN. We conducted a meta-analysis of randomized controlled trials (RCTs) of empirical therapy with echinocandins and non-echinocandins for FN in patients with hematological disease. The primary outcome was all-cause mortality within 7 days after completion of therapy. Secondary outcomes included treatment success, and discontinuation of therapy because of adverse events. For subgroup analysis, we compared RCTs of echinocandins with liposomal amphotericin B. Six RCTs (four that evaluated caspofungin and two that evaluated micafungin) were included in the meta-analysis. Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with non-echinocandins [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.49–0.99; RR 0.48, 95% CI 0.33–0.71, respectively]. There was no significant difference in treatment success (RR 1.09, 95% CI 0.87–1.36). Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with liposomal amphotericin B (RR 0.68, 95% CI 0.46–0.99; RR 0.53, 95% CI 0.37–0.74, respectively). In conclusion, patients with persistent FN treated with echinocandins had decreased risk of death and adverse events. Both caspofungin and micafungin may be recommended as first-line empirical antifungal therapy in these patients. However, the small number of enrolled patients and the lack of RCTs involving pediatric patients should be considered when using micafungin.

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Characterization of Bovine Lactoferrin Nanoparticle Prepared by Desolvation Technique.

Taguchi K, Chuang VTG, Hashimoto M, Nakayama M, Sakuragi M, Enoki Y, Nishi K, Matsumoto K, Seo H, Otagiri M, Yamasaki K

Chemical & pharmaceutical bulletin (公益社団法人日本薬学会) 68 ( 8 ) 766 - 772 2020

Research paper (scientific journal), Joint Work, Accepted, ISSN 0009-2363

<p>Lactoferrin (Lf) nanoparticles have been developed as a carrier of drugs and gene. Two main methods, desolvation technique and emulsification method, for preparation of protein nanoparticles have been reported so far, but most of the previous reports of Lf nanoparticles preparation are limited to emulsification method. In this study, we investigated the optimal conditions by desolvation technique for the preparation of glutaraldehyde-crosslinked bovine Lf (bLf) nanoparticles within the size range of 100–200 nm, and evaluated their properties as a carrier for oral and intravenous drug delivery. The experimental results of dynamic light scattering and Transmission Electron Microscope suggested that glutaraldehyde-crosslinked bLf nanoparticles with 150 nm in size could be produced by addition of 2-propanol as the desolvating solvent into the bLf solution adjusted to pH 6, followed by crosslinking with glutaraldehyde. These cross-linked bLf nanoparticles were found to be compatible to blood components and resistant against rapid degradation by pepsin. Thus, cross-linked bLf nanoparticles prepared by desolvation technique can be applied as a drug carrier for intravenous administration and oral delivery.</p>

Echinocandins versus non-echinocandins for the treatment of invasive candidiasis: A meta-analysis of randomized controlled trials

Tashiro S, Osa S, Igarashi Y, Watabe Y, Liu X, Enoki Y, Taguchi K, Mayumi T, Miyazaki Y, Takesue Y, Matsumoto K

Journal of Infection and Chemotherapy (Journal of Infection and Chemotherapy) 26 ( 11 ) 1164 - 1176 2020

Research paper (scientific journal), Joint Work, Accepted, ISSN 1341321X

© 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Introduction: Echinocandins are frequent use antifungals in the treatment of invasive candidiasis, and it is important to update information on their efficacy and safety for optimal antifungal drug treatment. The aim of this study is to clarify whether echinocandins are superior to non-echinocandins for the treatment of invasive candidiasis. Methods: We conducted a meta-analysis of RCTs of echinocandins and non-echinocandins for adult invasive candidiasis. The MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases before June 2019 were used. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method random-effects model. Results: We identified 14,846 articles and screened, and five studies were included meta-analysis. The treatment success ratio for echinocandins was significantly higher than that for non-echinocandins (RR = 1.14, 95% CI 1.06–1.22, p = 0.0003). In regard to adverse events, there was no significant difference between the two treatment groups. A subgroup analysis showed that the treatment success ratio for echinocandins was significantly higher than that for azoles (RR = 1.20, 1.08–1.34, p = 0.001), whereas no significant differences were observed between echinocandins and polyenes. In safety analysis, the incidence ratio of electrolyte disorder (RR = 0.50, 0.33–0.76, p = 0.001), renal disorder (RR = 0.19, 0.09–0.40, p < 0.0001), and fever (RR = 0.46, 0.23–0.93, p = 0.03) were significantly lower in patients receiving echinocandins than in those receiving polyenes. Conclusions: This meta-analysis based on RCTs was first to show that use of echinocandins was associated with improved clinical success. Echinocandins may be useful as a first-line drug for invasive candidiasis.

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Experimental verification of factors influencing calcium salt formation based on a survey of the development of ceftriaxone-induced gallstone-related disorder

Ito R, Yoshida A, Taguchi K, Enoki Y, Yokoyama Y, Matsumoto K

Journal of Infection and Chemotherapy (Journal of Infection and Chemotherapy) 25 ( 12 ) 972 - 978 2019.12

Research paper (scientific journal), Accepted, ISSN 1341321X

© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Ceftriaxone (CTRX) forms salts with calcium (Ca) in the gall bladder and bile duct, and induces the formation of gallstones. In this study, factors of CTRX-induced gallstone formation were extracted from the results of a retrospective survey using the Japanese Adverse Drug Event Report (JADER), and the causal relationship between the factors and gallstone formation was investigated. From JADER, 136 patients who developed ‘gallstone-related disorder’ with CTRX as a suspected drug were extracted. The incidence of gallstone-induced adverse effects was high in patients treated with CTRX at a dose exceeding the normal daily dose and in children younger than 10 years old, suggesting that CTRX at a high level is a factor for gallstone formation. Thus, after mixing CTRX and Ca2+ at different concentrations under different pH condition, the number of particles in the solutions was measured using a Coulter counter. As a result, the number of minute particles significantly increased at all pH values when Ca2+ and CTRX were mixed at a concentration of 10 mEq/L or higher and 1.5 g/L or higher, resp

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A selection table for information on heparinoid-containing preparation

Ishiwatari R, Enoki Y, Yokoyama Y, Taguchi K, Kizu J, Matsumoto K

Journal of Geriatric Pharmacy (Japanese Society of Geriatric Pharmacy) 2 ( 2 ) 19 - 26 2019.09

Research paper (scientific journal), Joint Work, Accepted

<p>We evaluated heparinoid-containing soft ointments and heparinoid-containing creams to develop information useful to select drugs. Spreadability, consistency and the water content of stratum corneum was measured. A selection table focusing on impression of the use was prepared. Spreadability of the semi-original soft ointment and cream were lower than those of all generic drugs. Regarding hardness, one generic soft ointment was softer than the semi-original drug, but the semi-original cream was harder than all generic creams. Regarding the impression of the use, a significant difference was noted in smell in soft ointments, and 6 items in creams. Correlation was found between the spreadability and consistency test results and impression of the use. A significant difference was noted in the water content of stratum corneum in creams. The selection table prepared based on the impression of the use may provide information that helps selection of preparations in clinical practice.</p>

Evaluation for optimal dosing of vancomycin in patients with different physical types

Hashimoto M, Iketani O, Ichinose N, Enoki Y, Taguchi K, Uno S, Uwamino Y, Hasegawa N, Matsumoto K

Journal of Infection and Chemotherapy (Journal of Infection and Chemotherapy) 25 ( 9 ) 735 - 737 2019.09

Research paper (scientific journal), Accepted, ISSN 1341321X

© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The sufficient dose to obtain an optimal trough concentration of vancomycin (VCM) in patients with non-standard physical types remains controversial. In this study, we examined the relationship between the dose and physical type in patients in whom an optimal trough concentration was obtained among VCM-treated patients. We retrospectively investigated the dose of VCM and physical type in patients treated with VCM between January 2012 and January 2017 at two medical institutions (n = 272). The physical type was classified using the body mass index (BMI). Patients with a BMI of <18.5 kg/m2 were assigned to the lean group, those with a BMI of 18.5–24.9 kg/m2 were assigned to the standard group, and those with a BMI of ≥25 kg/m2 were assigned to the obesity group. The mean doses of VCM per time (mg/kg) to achieve the target trough concentration of VCM, 15–20 μg/mL, were 19.8 ± 4.3, 16.5 ± 3.7, and 13.7 ± 2.7 mg/kg in the lean, standard, and obesity groups, respectively. The dose per time to achieve the target trough concentration decreased significantly in association with an increas

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リネゾリド血中濃度上昇に伴い低ナトリウム血症が発現した症例

田口和明, 榎木裕紀, 松元一明, 池谷修, 宇野俊介, 上蓑義典, 長谷川直樹

日本化学療法学会雑誌 ((公社)日本化学療法学会) 67 ( Suppl.A ) 292 - 292 2019.03

Accepted, ISSN 1340-7007

ダプトマイシンによりクレアチニンキナーゼが上昇した肥満患者

榎木裕紀, 山本理紗子, 佐村優, 田口和明, 松元一明

第67回日本化学療法学会総会 (日本化学療法学会) 67 ( Suppl.A ) 292 - 292 2019.03

ISSN 1340-7007

リネゾリドにより低ナトリウム血症から痙攣を発症した患者

山本冴華, 田口和明, 榎木裕紀, 松元一明, 池谷修, 宇野俊介, 上蓑義典, 長谷川直樹

日本薬学会年会要旨集 ((公社)日本薬学会) 139年会 ( 4 ) 131 - 131 2019.03

ISSN 0918-9823

リネゾリドにより低ナトリウム血症から痙攣を発症した患者

山本冴華, 田口和明, 榎木裕紀, 松元一明, 池谷修, 宇野俊介, 上蓑義典, 長谷川直樹

日本薬学会年会要旨集 ((公社)日本薬学会) 139年会 ( 4 ) 131 - 131 2019.03

Accepted, ISSN 0918-9823

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