title: A single intramuscular injection of neuraminidase inhibitor peramivir demonstrates antiviral activity against novel pandemic A/California/04/2009 (H1N1) influenza virus infection in mice.
abstract: New and emerging influenza virus strains, such as the pandemic influenza A (H1N1) virus require constant vigilance for antiviral drug sensitivity and resistance. Efficacy of intramuscularly (IM) administered neuraminidase (NA) inhibitor, peramivir, was evaluated in mice infected with recently isolated pandemic A/California/04/2009 (H1N1, swine origin, mouse adapted) influenza virus. A single IM injection of peramivir (four dose groups), given 1h prior to inoculation, significantly reduced weight loss (p < 0.001) and mortality (p < 0.05) in mice infected with LD90 dose of pandemic A/California/04/2009 (H1N1) influenza virus compared to vehicle group. There was 20% survival in the vehicle-treated group, whereas in the peramivir-treated groups, survival increased in a dose-dependent manner with 60, 60, 90 and 100% survivors for the 1, 3, 10, and 30 mg/kg doses, respectively. Weight loss on day 4 in the vehicle-treated group was 3.4 gm, and in the peramivir-treated groups was 2.1, 1.5, 1.8 and 1.8 g for the 1, 3, 10 and 30 mg/kg dose groups, respectively. In the treatment model, peramivir given 24h after infection as a single IM injection at 50mg/kg dose, showed significant protection against lethality and weight loss. There was 13% survival in the vehicle-treated group while in the peramivir-treated group at 24, 48, and 72 h post infection, survival was 100, 40, and 50%, respectively. Survival in the oseltamivir groups (10 mg/kg/d twice a day, orally for 5 days) was 90, 30 and 20% at 24, 48 and 72 h, respectively. These data demonstrate efficacy of parenterally administered peramivir against the recently isolated pandemic influenza virus in murine infection models.
authors.affiliation: BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA. sbantia@biocryst.com
authors.forename: Shanta
authors.initials: S
authors.lastname: Bantia
authors.forename: Debra
authors.initials: D
authors.lastname: Kellogg
authors.forename: Cynthia
authors.initials: C
authors.lastname: Parker
authors.forename: Ramanda
authors.initials: R
authors.lastname: Upshaw
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ilyushina
authors.forename: Y S
authors.initials: YS
authors.lastname: Babu
mesh_terms: D000146:Acids, Carbocyclic; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D001835:Body Weight; D003517:Cyclopentanes / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines / Q000008:administration & dosage*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000821:virology; D012376:Rodent Diseases / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000821:virology; D016019:Survival Analysis
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; C414210:peramivir