Efficacy of single intravenous injection of peramivir against influenza B virus infection in ferrets and cynomolgus macaques.

Abstract

We evaluated the efficacy of a single intravenous dose peramivir for treatment of influenza B virus infection in ferrets and cynomolgus macaques in the present study. A single dose of peramivir (60 mg/kg of body weight) given to ferrets on 1 day postinfection with influenza B virus significantly reduced median area under the curve (AUC) virus titers (peramivir, 8.3 log(10) 50% tissue culture infective doses [TCID(50)s] · day/ml; control, 10.7 log(10) TCID(50)s · day/ml; P < 0.0001). Furthermore, nasal virus titers on day 2 postinfection in ferrets receiving a single injection of peramivir (30 mg/kg) and AUCs of the body temperature increase in ferrets receiving a single injection of peramivir (30 and 60 mg/kg) were lower than those in ferrets administered oral oseltamivir phosphate (30 and 60 mg/kg/day twice daily for 3 days). In macaques infected with influenza B virus, viral titers in the nasal swab fluid on days 2 and 3 postinfection and body temperature after a single injection of peramivir (30 mg/kg) were lower than those after oral administration of oseltamivir phosphate (30 mg/kg/day for 5 days). The two animal models used in the present study demonstrated that inhibition of viral replication at the early time point after infection was critical in reduction of AUCs of virus titers and interleukin-6 production, resulting in amelioration of symptoms. Our results shown in animal models suggest that the early treatment with a single intravenous injection of peramivir is clinically recommended to reduce symptoms effectively in influenza B virus infection.

• Authors: Mitsutaka Kitano, Yasushi Itoh, Makoto Kodama, Hirohito Ishigaki, Misako Nakayama, Hideaki Ishida, Kaoru Baba, Takahiro Noda, Kenji Sato, Yoichiro Nihashi, Takushi Kanazu, Ryu Yoshida, Ryuzo Torii, Akihiko Sato, Kazumasa Ogasawara
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 55 Issue 11 Pg. 4961-70 (Nov 2011) ISSN: 1098-6596 [Electronic] United States
• PMID: 21844317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acids, Carbocyclic
• Cyclopentanes
• Guanidines
• peramivir

Topics

• Acids, Carbocyclic
• Animals
• Cyclopentanes (administration & dosage, therapeutic use)
• Ferrets (virology)
• Guanidines (administration & dosage, therapeutic use)
• Influenza B virus (drug effects, pathogenicity)
• Injections, Intravenous
• Macaca (virology)
• Orthomyxoviridae Infections (drug therapy, virology)