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Antimicrob Agents Chemother. Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice

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  • Antimicrob Agents Chemother. Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice

    [Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
    Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice


    Mitsutaka Kitano 1,3, Makoto Kodama 1, Yasushi Itoh 3, Takushi Kanazu 2, Masanori Kobayashi 1, Ryu Yoshida 1 and Akihiko Sato 1,*

    Author Affiliations: <SUP>1</SUP>Infectious Diseases, Medicinal Research Laboratories <SUP>2</SUP>Drug Metabolism & Pharmacokinetics, Drug Developmental Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Osaka, 561-0825 <SUP>3</SUP>Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan



    ABSTRACT

    The efficacy of intravenous peramivir against influenza A (H1N1) 2009 virus infection was evaluated in mice of which immune system was suppressed by cyclophosphamide (CP) treatment. The mortality rate of the vehicle control group was 100% and the mice lost 20% of their body weight on average by day 13 post infection (p.i.). Repeated administration of peramivir (40 mg/kg once a day, intravenously for 20 days), starting at 1 h p.i., significantly reduced mortality, body weight loss, viral titers, and cytokine production in infected mice compared with the vehicle administration (p < 0.01). In addition, repeated administration of peramivir, starting at 24 h, 48 h, or 72 h p.i. also resulted in increases in survival rates and reduction of viral titers in the lungs (p < 0.01). The mean days-to-death (MDD) of the vehicle group was 14.5 days, while in the groups treated with peramivir starting at 24 h, 48 h, and 72 h p.i., the MDDs were > 23.0, 20.9, and 21.8 days, respectively. In comparison, repeated administration of oseltamivir phosphate (5 mg/kg twice a day, orally for 20 days), starting at 24 h, 48 h, and 72 h p.i., also significantly prevented body weight loss, whereas no significant differences in mortality rates and viral titers in the lungs were observed when compared with the vehicle group. These data indicated that repeated administration of peramivir was effective in promoting the survival and reducing virus replication in immunosuppressed mice infected with influenza A (H1N1) 2009 virus.



    FOOTNOTES

    *Corresponding author Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd. 3-1-1, Futabacho, Toyonaka, Osaka 561-0825, Japan. Tel: +81 (6) 6331 7239, Fax: +81 (6) 6332 6385, E-mail: akihiko.sato@shionogi.co.jp

    Copyright 2013, American Society for Microbiology. All Rights Reserved.
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