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.