title: Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice.
abstract: The efficacy of intravenous peramivir against influenza A (H1N1) 2009 virus infection was evaluated in mice in which the 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 postinfection (p.i.). Repeated administration of peramivir (40 mg/kg of body weight once a day, given 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 results for administration of vehicle (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, given 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 compared with results for 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.
authors.affiliation: Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Kitano
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.forename: Takushi
authors.initials: T
authors.lastname: Kanazu
authors.forename: Masanori
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ryu
authors.initials: R
authors.lastname: Yoshida
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
mesh_terms: D000146:Acids, Carbocyclic; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000254:growth & development; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000494:pharmacology; D010757:Phosphorous Acids / Q000494:pharmacology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D007166:Immunosuppressive Agents; D010757:Phosphorous Acids; C530824:tamiphosphor; D053139:Oseltamivir; D003520:Cyclophosphamide; C414210:peramivir