Papers - Yokoyama, Yuta

Prognostic Value of Baseline Medications plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients with Advanced Non-Small-Cell Lung Cancer: A Retrospective Study. Frontiers in Oncology

Ogiwara T., Kawazoe H., Egami S., Hashimoto H., Saito Y., Sakiyama N., Ohe Y., Yamaguchi M., Furukawa T., Hara A., Hiraga Y., Jibiki A., Yokoyama Y., Suzuki S., Nakamura T.

Frontiers in Oncology 11   770268 2021

Research paper (scientific journal), Joint Work, Accepted

薬学教育モデル・コアカリキュラムに基づく実務実習におけるルーブリック形式の概略評価は実習生のパフォーマンスレベルを測定できるか？

河添　仁、鈴木小夜、平賀ゆい、横山雄太、地引綾、岩田紘樹、小林典子、藤本和子、中田英夫、青森達、 山浦克典、中村智徳

医療薬学 47   513 - 524 2021

Research paper (scientific journal), Joint Work, Accepted

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

Journal of Pharmacy and Pharmacology (Journal of Pharmacy and Pharmacology)  72 ( 10 ) 1361 - 1369 2020.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00223573

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© 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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Pharmacokinetic/pharmacodynamic 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 38 ( 1 ) 83 - 87 2020

Research paper (scientific journal), Joint Work, Accepted

代表的8疾患と薬局実習が病院実習の到達度に与える影響

清宮啓介, 津田壮一郎, 池淵由香, 鈴木小夜, 地引綾, 岩田紘樹, 横山雄太, 河添仁, 小林典子, 藤本和子, 山浦克典, 中村智徳, 村松博, 青森達, 望月眞弓

医療薬学 46   715 - 721 2020

Research paper (scientific journal), Joint Work, Accepted

実務実習生の薬学専門科目に対する自己効力感は実務実習での成功体験に影響を与える

菊山史博, 鈴木小夜, 地引綾, 横山雄太, 河添仁, 中村智徳

薬学雑誌 ((公社)日本薬学会)  140 ( 6 ) 799 - 808 2020

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0031-6903

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実務実習生の薬学専門科目に対する自己効力感(「得意である」という心理)が患者に貢献した成功体験に及ぼす影響を明らかにした。実務実習生299名を対象に、実習直前の説明会(以下、実習前)、I期実務実習後(以下、I期後)およびII期実務実習後(以下、II期後)の3時点でアンケート調査を実施した。I期後およびII期後の得意値はそれぞれ実習前より上昇した。I期病院実習群では得意値が上昇した人、すなわち得意値の変化量が正であった場合に成功体験を経験した実習生が多かったが、I期薬局実習群では得意値の変化量の違いによる成功体験の有無に差は認められなかった。パス解析の結果、I期病院実習生において「基礎科学」や「衛生薬学」が成功体験に対する有意な正の影響要因、「薬物治療学」は負の影響要因であり、標準化係数の絶対値は正の影響要因を示した「基礎科学」や「衛生薬学」よりも大きかった。成功体験に関する記述の対応分析の結果、I期およびII期薬局実習生の成功体験が医療従事者より患者を対象に記述する傾向があった。I期病院実習生の成功体験に関する記述は医療従事者を記述する傾向があり、「薬」や「処方」の「提案」、「減量」または「変更」などが近位に表出され専門知識が直接的に必要と推測される成功体験であったと推測された。

デキサメタゾン配合後における先発及び後発医薬品のゲムシタビン注射剤の製剤学的安定性の評価

吉浦誠海, 河添仁, 鈴木小夜, 横山雄太, 地引綾, 中村智徳

日本臨床腫瘍薬学会雑誌 14   1 - 7 2020

Research paper (scientific journal), Joint Work, Accepted

Renal dysfunction and anemia associated with long-term imatinib treatment in patients with chronic myelogenous leukemia.

Sakurai M, Kikuchi T, Karigane D, Kasahara H, Matsuki E, Hashida R, Yamane Y, Abe R, Koda Y, Toyama T, Kato J, Shimizu T, Yokoyama Y, Suzuki S, Nakamura T, Okamoto S, Mori T

International Journal of Hematology (International Journal of Hematology)  109 ( 3 ) 292 - 298 2019.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09255710

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© 2019, Japanese Society of Hematology. Knowledge of the toxicity profile of long-term treatment with imatinib is limited. In the present study, we sought to evaluate renal function and hemoglobin levels during long-term imatinib treatment. Eighty-two patients with chronic myelogenous leukemia in chronic phase who had been on imatinib for over 5 years were retrospectively analyzed. The mean estimated glomerular filtration rate (eGFR) was significantly decreased over 5 years (77 ± 17 to 62 ± 14 ml/min/1.73m², P < 0.001). Higher age and lower eGFR value at initiation of imatinib were significantly associated with development of renal dysfunction by multivariate analyses. Mean hemoglobin levels also significantly decreased over the 5-year period (12.9 ± 1.7 to 12.4 ± 1.3 g/dl, P < 0.01). The rate of decrease in eGFR correlated significantly with hemoglobin levels (correlation coefficient = − 0.249, P < 0.05). Serum erythropoietin (EPO) levels did not increase in 16 patients with both renal dysfunction and anemia (median, 31.9 mIU/ml). In patients who participated in a clinical trial of imatinib discontinuation, mean eGFR (50.0 ± 6.5 to 56.0 ± 10.2 ml/min/1.73m², P < 0.05) and hemoglobin levels (12.0 ± 1.7 to 14.0 ± 1.6 g/dl, P < 0.01) improved significantly at 1 year after discontinuation. These findings suggest that long-term imatinib results in a partially reversible continuous decline in renal function and decreased hemoglobin levels.

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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

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

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© 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, respectively. At pH 6.5 or 7.0, visible crystals were detected when 25 mEq/L of Ca2+ and 2.0 g/L of CTRX were mixed. Based on these findings, attention should be sufficiently paid to the development of ‘gallstone-related disorder’ in pediatric patients and in patients treated with CTRX at a dose exceeding the normal dose. Furthermore, gallstone formation and growth may be promoted when CTRX and Ca2+ coexist at high concentrations under low pH conditions.

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A Selection Table for Information on Heparinoid-Containing Preparation

Ishiwatari Ryoko, Enoki Yuki, Yokoyama Yuta, Taguchi Kazuaki, Kizu Junko, Matsumoto Kazuaki

Journal of Geriatric Pharmacy (Japanese Society of Geriatric Pharmacy)  2 ( 2 ) 19 - 26 2019

Research paper (scientific journal), Joint Work, Accepted

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<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>

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改訂薬学教育モデル・コアカリキュラムに準拠した実務実習に向けたルーブリック形式の概略評価を用いたパフォーマンス評価の先行導入：学生視点に基づくアウトカム評価と教育効果向上のための提案

鈴木小夜, 河添仁, 地引綾, 横山雄太, 中村智徳

医療薬学 45   228 - 239 2019

Research paper (scientific journal), Joint Work, Accepted

Evaluation of the expression time of ganciclovir-induced adverse events using JADER and FAERS

Ando G, Taguchi K, Enoki Y, Yokoyama Y, Kizu J, Matsumoto K

Biological and Pharmaceutical Bulletin (Biological and Pharmaceutical Bulletin)  42 ( 11 ) 1799 - 1804 2019

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09186158

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© 2019 The Pharmaceutical Society of Japan. Investigation of the occurrence time of adverse drug reactions helps to prevent the development and aggravation of adverse reactions, but the expression time of ganciclovir-induced adverse events has not been elucidated. In this study, using databases of spontaneous adverse event reports, the Japanese Adverse Drug Event Report database (JADER) and the U.S. Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS), the incidence of adverse reactions due to ganciclovir and their expression time were analyzed. As a result of calculation of the reporting odds ratio (ROR) and 95% confidence interval for individual main adverse reactions of ganciclovir (cytopenia, leukopenia, thrombocytopenia, liver damage, and acute renal failure), a signal was detected for all adverse reactions in both databases, except for liver damage in JADER. Furthermore, the Weibull distribution was performed for the analysis of onset time of each ganciclovir-induced adverse event. The results of Weibull parameter α and β values of each adverse event in both JADER and FAERS suggested that most adverse events occurred within 30 d and classified into the early failure type, except that thrombocytopenia and acute renal failure in JADER classified into the random failure type. Based on these findings, it concluded that the paying attention to signs of each ganciclovirinduced adverse event is required from the early phase after ganciclovir administration. However, in FAERS, development after a long-term course also accounted for 11%, suggesting that long-term periodic monitoring of adverse reactions would be also required.

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Dosing optimization of meropenem based on a pharmacokinetic analysis in patients receiving hemodiafiltration and an in vitro model.

Yokoyama Y., Nishino K., Matsumoto K., Inomoto Y., Matsuda K., Nakamura R., Yasuno N., Kizu J.

Journal of Infection and Chemotherapy (Journal of Infection and Chemotherapy)  24 ( 2 ) 92 - 98 2018

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

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© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The purpose of this study was to estimate the in vivo pharmacokinetics of meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its optimal dosage and dosing interval in patients receiving I-HDF. The clearance of meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an in vitro system and assessed to establish whether the results obtained are applicable to clinical cases. In the in vivo study, the mean volume of distribution (Vd), non-I-HDF clearance (CLnon-I-HDF), and I-HDF clearance (CLI-HDF) were 15.80 ± 3.59 l, 1.05 ± 0.27 l/h, and 5.78 ± 1.03 l/h. Dosing regimens of 0.25 g once daily for a MIC of 8 μg/ml and of 0.5 g once daily for a MIC of 16 μg/ml achieved 40% T > MIC. In the in vitro and in vivo studies, observed CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). In conclusion, adjustments to the dose and interval of meropenem were developed based on the presumed susceptibility of pathogens to meropenem in patients receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for empirical treatment.

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Development of HPLC with fluorescent detection using NBD-F for the quantification of colistin sulfate in rat plasma and its pharmacokinetic applications.

16. Ouchi S, Matsumoto K, Okubo M, Yokoyama Y, Kizu J.

Biomedical Chromatography (Biomedical Chromatography)  32 ( 5 ) e4167 2018

Research paper (scientific journal), Joint Work, Accepted,  ISSN  02693879

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Copyright © 2017 John Wiley & Sons, Ltd. Colistin sulfate, composed of a mixture of colistin A sulfate (CLA) and colistin B sulfate (CLB), is available for treating life-threatening infections caused by multidrug-resistant Gram-negative bacteria. In this study, the CLA and CLB were quantified separately. Colistin sulfate was extracted from rat plasma with a solid-phase extraction C18 cartridge and reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and the fluorescent derivatives were subjected to reversed-phase high-performance liquid chromatography analysis and used to investigate the pharmacokinetics of CLA and CLB in rat plasma. The recovery rates of CLA and CLB were 41.2 ± 4.4 and 45.5 ± 3.1%, respectively. The recovery rate calculated from the total area of CLA and CLB was 43.9 ± 3.6%. When 2 mm NBD-F and 10 mm boric acid buffer (pH 9.5) were added to colistin sulfate, the highest recovery rate was obtained. The best heating time was 5 min at 60°C. The lower limits of quantification for CLA, CLB and the total area of CLA and CLB were 0.05, 0.05 and 0.1 μg/mL; the coefficients of variations were 13.5, 14.5 and 14.1%, respectively. This method was found to have acceptable linearity, precision and accuracy, and has been successfully applied to a pharmacokinetic study in rat plasma.

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抗菌薬のTDM実施に関する実態調査－感染制御体制とTDM実施率の相関ならびに抗菌薬TDMガイドラインとの比較－.

松元一明, 磯田梨奈, 黒田裕子, 横山雄太, 木津純子.

日本化学療法学会雑誌 65 ( 2 ) 175 - 182 2017.03

Research paper (scientific journal), Joint Work, Accepted

ラモトリギンの医薬品副作用データおよび医薬品副作用被害救済給付決定情報の調査解析.

横山雄太, 黒田裕子, 安藤剛, 松元一明, 木津純子.

日本病院薬剤師会雑誌 53 ( 3 ) 283 - 289 2017.03

Research paper (scientific journal), Joint Work, Accepted

Synthesis of linezolid metabolites PNU-142586 and PNU-142300 toward the exploration of metabolite-related events.

Kengo Hanaya, Kazuaki Matsumoto, Yuta Yokoyama, Junko Kizu, Mitsuru Shoji, Takeshi Sugai.

CHEMICAL & PHARMACEUTICAL BULLETIN 65 ( 2 ) 194 - 199 2017.02

Research paper (scientific journal), Joint Work, Accepted

有害事象自発報告データベース（JADER）からみた医薬品による交通事故.

安藤剛, 松元一明, 横山雄太, 木津純子.

日本交通科学協議会誌 16 ( 1 ) 46 - 51 2017.01

Research paper (scientific journal), Joint Work, Accepted

Factorial analysis of hepatitis B virus reactivation-induced hepatitis B using JADER.

Ayako Hara, Kazuaki Matsumoto, Yuta Yokoyama, Junko Kizu.

BIOLOGICAL & PHARMACEUTICAL BULLETIN 40 ( 6 ) 782 - 788 2017

Research paper (scientific journal), Joint Work, Accepted

CYP2C19遺伝子多型と代謝物濃度をふまえたTDMによるボリコナゾール投与量適正化が有用であった2例.

茂見茜里, 松元一明, 渡辺英里香, 猪川和朗, 金澤直子, 横山雄太, 梅﨑靖弘, 池田龍二, 森川則文, 武田泰生

日本外科感染症学会雑誌 13   661 - 667 2016.12

Research paper (scientific journal), Joint Work, Accepted