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The therapeutic effectiveness of arbekacin is directly related to Cmax at the infection site. To maximize drug delivery to the respiratory tract and minimize the systemic toxicity, arbekacin optimized for inhalation, ME1100, is under development. In this study, we investigated the efficacy and pharmacokinetics of ME1100 in a murine model of ventilator-associated pneumonia caused by P. aeruginosa by using a customized investigational nebulizer system. Methods: The mice were treated for 5 min, once daily, with placebo, 3, 10 or 30 mg/mL ME1100 or 30 mg/mL amikacin. Results: In the survival study, the survival rate was significantly improved in the 10 and 30 mg/mL ME1100 treatment groups compared with that in the placebo group. The number of bacteria in the lungs was significantly lower in the 30 mg/mL ME1100 treatment group at 6 h after the initial treatment, compared with all other groups. 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Efficacy and pharmacokinetics of ME1100, a novel optimized formulation of arbekacin for inhalation, compared with amikacin in a murine model of ventilator-associated pneumonia caused by Pseudomonas aeruginosa
http://hdl.handle.net/10069/00040541
http://hdl.handle.net/10069/00040541d01dbf82-aeda-45a0-ae9f-4c59201a40cb
名前 / ファイル | ライセンス | アクション |
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JAC72_1123.pdf (677.9 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-03-12 | |||||
タイトル | ||||||
タイトル | Efficacy and pharmacokinetics of ME1100, a novel optimized formulation of arbekacin for inhalation, compared with amikacin in a murine model of ventilator-associated pneumonia caused by Pseudomonas aeruginosa | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kaku, Norihito
× Kaku, Norihito× Morinaga, Yoshitomo× Takeda, Kazuaki× Kosai, Kosuke× Uno, Naoki× Hasegawa, Hiroo× Miyazaki, Taiga× Izumikawa, Koichi× Mukae, Hiroshi× Yanagihara, Katsunori |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background: Arbekacin is an aminoglycoside that shows strong antimicrobial activity against Gram-positive bacteria, including MRSA, as well as Pseudomonas aeruginosa. The therapeutic effectiveness of arbekacin is directly related to Cmax at the infection site. To maximize drug delivery to the respiratory tract and minimize the systemic toxicity, arbekacin optimized for inhalation, ME1100, is under development. In this study, we investigated the efficacy and pharmacokinetics of ME1100 in a murine model of ventilator-associated pneumonia caused by P. aeruginosa by using a customized investigational nebulizer system. Methods: The mice were treated for 5 min, once daily, with placebo, 3, 10 or 30 mg/mL ME1100 or 30 mg/mL amikacin. Results: In the survival study, the survival rate was significantly improved in the 10 and 30 mg/mL ME1100 treatment groups compared with that in the placebo group. The number of bacteria in the lungs was significantly lower in the 30 mg/mL ME1100 treatment group at 6 h after the initial treatment, compared with all other groups. In the pharmacokinetic study, the Cmax in the 30 mg/mL ME1100 treatment group in the epithelial lining fluid (ELF) and plasma was 31.1 and 1.2 mg/L, respectively. Furthermore, we compared the efficacy of ME1100 with that of amikacin. Although there were no significant differences in ELF and plasma concentrations between 30 mg/mL of ME1100 and 30 mg/mL of amikacin, ME1100 significantly improved the survival rate compared with amikacin. Conclusions: The results of our study demonstrated the in vivo effectiveness of ME1100 and its superiority to amikacin. | |||||
書誌情報 |
Journal of Antimicrobial Chemotherapy 巻 72, 号 4, p. 1123-1128, 発行日 2017-04 |
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出版者 | ||||||
出版者 | Oxford University Press | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0305-7453 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1093/jac/dkw517 | |||||
権利 | ||||||
権利情報 | © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record Journal of Antimicrobial Chemotherapy, 72(4), pp.1123-1128; 2017 is available online at: https://doi.org/10.1093/jac/dkw517. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal of Antimicrobial Chemotherapy, 72(4), pp.1123-1128; 2017 |