title: Evaluation of intravenous zanamivir against experimental influenza A (H5N1) virus infection in cynomolgus macaques.
abstract: We investigated the prophylactic and therapeutic efficacy of an intravenous (IV) formulation of zanamivir in a macaque infection model for highly pathogenic influenza A (H5N1) virus. Antiviral efficacy was dose-dependent, with no reduction in viral load observed at 2 mg/kg, but a significant reduction observed at 10 mg/kg (p=0.039) and at 20 mg/kg in the combined prophylactic and therapeutic groups (p=0.049) with both prophylaxis (commencing 12 h before infection) and therapy (commencing 4 h after infection) showing similar reductions in viral load. Combined gross pathology and microscopic pneumonia scores in the treated animals relative to untreated controls were significantly reduced at 10 mg/kg (p=0.02) and at 20 mg/kg in the prophylaxis group (p=0.02), but were not significant in the treatment group (p=0.145). In this new animal model for evaluation of influenza antivirals, despite variability observed between individual animals, IV zanamivir showed evidence of efficacy against highly pathogenic H5N1 virus.
authors.affiliation: ViroClinics BV, Rotterdam, The Netherlands.
authors.forename: K J
authors.initials: KJ
authors.lastname: Stittelaar
authors.forename: M
authors.initials: M
authors.lastname: Tisdale
authors.forename: G
authors.initials: G
authors.lastname: van Amerongen
authors.forename: R F
authors.initials: RF
authors.lastname: van Lavieren
authors.forename: F
authors.initials: F
authors.lastname: Pistoor
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: A D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D008251:Macaca; D008297:Male; D053243:Zanamivir / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D053243:Zanamivir