論文 - 横山　雄太

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年

研究論文（学術雑誌）, 共著, 査読有り

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年

研究論文（学術雑誌）, 共著, 査読有り

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年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00223573

　概要を見る

© 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年

研究論文（学術雑誌）, 共著, 査読有り

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年

研究論文（学術雑誌）, 共著, 査読有り

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年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0031-6903

　概要を見る

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年

研究論文（学術雑誌）, 共著, 査読有り

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年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09255710

　概要を見る

© 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年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1341321X

　概要を見る

© 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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ヘパリン類似物質含有製剤の選択に有用な情報構築に関する検討

石渡涼子、榎木裕紀、横山雄太、田口和明、木津純子、松元一明

日本老年薬学会雑誌 （(一社)日本老年薬学会）  2 （ 2 ） 19 - 26 2019年

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

保湿剤として臨床現場で汎用されているヘパリン類似物質ソフト軟膏5銘柄(A、B、C、D、E)とクリーム6銘柄(F、G、H、I、J、K)を用いて、患者に適した薬剤を選択する際に役立つ情報を構築するために、製剤学的特性(展延性、稠度)、使用感および角質水分量の変化に関する研究を行った。ソフト軟膏ではAの延びが最も低く、最も軟らかい製剤はEであった。クリーム製剤ではFの延びが最も低く、最も硬い製剤はFであった。ソフト軟膏製剤間の使用感比較では、最も使いやすいとされた製剤、使いにくいとされた製剤はいずれもDであり、クリーム製剤では最も使いやすいとされたのはJ、最も使いにくいとされたのはHであった。ソフト軟膏塗布後の角質水分量の変化量に関して銘柄間で差はみられず、クリーム製剤では銘柄Fが銘柄JおよびKと比較して有意に角質水分量の増加がみられた。

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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年

研究論文（学術雑誌）, 共著, 査読有り

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年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09186158

　概要を見る

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

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

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

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  02693879

　概要を見る

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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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年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り,  ISSN  1341321X

　概要を見る

© 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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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年03月

研究論文（学術雑誌）, 共著, 査読有り

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年03月

研究論文（学術雑誌）, 共著, 査読有り

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年02月

研究論文（学術雑誌）, 共著, 査読有り

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年01月

研究論文（学術雑誌）, 共著, 査読有り

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年

研究論文（学術雑誌）, 共著, 査読有り

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年12月

研究論文（学術雑誌）, 共著, 査読有り