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Antimicrob Agents Chemother. 2014 Jun 9. pii: AAC.02817-14. [Epub ahead of print]
Efficacy of repeated intravenous administration of peramivir against highly pathogenic avian influenza A (H5N1) virus in cynomolgus macaques.
Kitano M1, Itoh Y2, Ishigaki H3, Nakayama M3, Ishida H3, Pham VL3, Arikata M3, Shichinohe S4, Tsuchiya H5, Kitagawa N3, Kobayashi M6, Yoshida R6, Sato A6, Le QM7, Kawaoka Y8, Ogasawara K3.
Author information
Abstract
Highly pathogenic avian influenza A (H5N1) viruses cause severe and often fatal disease in humans. We evaluated the efficacy of repeated intravenous dosing of a neuraminidase inhibitor peramivir against highly pathogenic avian influenza virus A/Vietnam/UT3040/2004 (H5N1) infection in cynomolgus macaques. Repeated dosing of peramivir (30 mg/kg/day once a day for 5 days) starting immediately after infection significantly reduced viral titers in the upper respiratory tract, body weight loss, and cytokine production and resulted in significant reduction in body temperature in infected macaques compared with those in macaques administered a vehicle (p < 0.05). Repeated administration of peramivir starting at 24 h after infection also resulted in reduction in viral titers and reduction in the period of virus detection in the upper respiratory tract although the difference of body temperature change was not statistically significant. The macaque model used in the present study demonstrated that inhibition of viral replication at an early time point after infection by repeated intravenous treatment with peramivir is critical for reduction of production of cytokines, i.e. IL-6, TNF-α, IFN-γ, MCP-1 and IL-12p40, resulting in amelioration of symptoms caused by highly pathogenic avian influenza virus infection.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24913156
[PubMed - as supplied by publisher]
Efficacy of repeated intravenous administration of peramivir against highly pathogenic avian influenza A (H5N1) virus in cynomolgus macaques.
Kitano M1, Itoh Y2, Ishigaki H3, Nakayama M3, Ishida H3, Pham VL3, Arikata M3, Shichinohe S4, Tsuchiya H5, Kitagawa N3, Kobayashi M6, Yoshida R6, Sato A6, Le QM7, Kawaoka Y8, Ogasawara K3.
Author information
Abstract
Highly pathogenic avian influenza A (H5N1) viruses cause severe and often fatal disease in humans. We evaluated the efficacy of repeated intravenous dosing of a neuraminidase inhibitor peramivir against highly pathogenic avian influenza virus A/Vietnam/UT3040/2004 (H5N1) infection in cynomolgus macaques. Repeated dosing of peramivir (30 mg/kg/day once a day for 5 days) starting immediately after infection significantly reduced viral titers in the upper respiratory tract, body weight loss, and cytokine production and resulted in significant reduction in body temperature in infected macaques compared with those in macaques administered a vehicle (p < 0.05). Repeated administration of peramivir starting at 24 h after infection also resulted in reduction in viral titers and reduction in the period of virus detection in the upper respiratory tract although the difference of body temperature change was not statistically significant. The macaque model used in the present study demonstrated that inhibition of viral replication at an early time point after infection by repeated intravenous treatment with peramivir is critical for reduction of production of cytokines, i.e. IL-6, TNF-α, IFN-γ, MCP-1 and IL-12p40, resulting in amelioration of symptoms caused by highly pathogenic avian influenza virus infection.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24913156
[PubMed - as supplied by publisher]
