Efficacy of repeated intravenous administration of peramivir against highly pathogenic avian influenza A (H5N1) virus in cynomolgus macaques.

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 the 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 a significant body temperature reduction in infected macaques compared with that of macaques administered a vehicle (P < 0.05). Repeated administration of peramivir starting at 24 h after infection also resulted in a reduction in viral titers and a reduction in the period of virus detection in the upper respiratory tract, although the 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 the production of cytokines, i.e., interleukin-6 (IL-6), tumor necrosis factor α, gamma interferon, monocyte chemotactic protein 1, and IL-12p40, resulting in amelioration of symptoms caused by highly pathogenic avian influenza virus infection.

• Authors: Mitsutaka Kitano, Yasushi Itoh, Hirohito Ishigaki, Misako Nakayama, Hideaki Ishida, Van Loi Pham, Masahiko Arikata, Shintaro Shichinohe, Hideaki Tsuchiya, Naoko Kitagawa, Masanori Kobayashi, Ryu Yoshida, Akihiko Sato, Quynh Mai Le, Yoshihiro Kawaoka, Kazumasa Ogasawara
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 8 Pg. 4795-803 (Aug 2014) ISSN: 1098-6596 [Electronic] United States
• PMID: 24913156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Acids, Carbocyclic
• Antiviral Agents
• Chemokine CCL2
• Cyclopentanes
• Guanidines
• Interleukin-12 Subunit p40
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• peramivir

Topics

• Acids, Carbocyclic
• Administration, Intravenous
• Animals
• Antiviral Agents (pharmacology)
• Body Temperature (drug effects)
• Body Weight (drug effects)
• Chemokine CCL2 (antagonists & inhibitors, biosynthesis)
• Cyclopentanes (pharmacology)
• Drug Administration Schedule
• Female
• Guanidines (pharmacology)
• Influenza A Virus, H5N1 Subtype (drug effects, pathogenicity, physiology)
• Interferon-gamma (antagonists & inhibitors, biosynthesis)
• Interleukin-12 Subunit p40 (antagonists & inhibitors, biosynthesis)
• Interleukin-6 (antagonists & inhibitors, biosynthesis)
• Macaca fascicularis
• Orthomyxoviridae Infections (drug therapy, physiopathology, veterinary, virology)
• Time Factors
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis)
• Virulence
• Virus Replication (drug effects)