tetano
Editor, Senior Moderator
Antiviral Res. 2012 Mar 10. [Epub ahead of print]
Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice.
Tarbet EB, Maekawa M, Furuta Y, Babu YS, Morrey JD, Smee DF.
Source
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, United States.
Abstract
Favipiravir, an influenza virus RNA polymerase inhibitor, and peramivir, an influenza virus neuraminidase inhibitor, were evaluated alone and in combination against pandemic influenza A/California/04/2009 (H1N1) virus infections in mice. Infected mice were treated twice daily for 5d starting 4h after virus challenge. Favipiravir was 40%, 70%, and 100% protective at 20, 40, and 100mg/kg/d. Peramivir was 30% protective at 0.5mg/kg/d, but ineffective at lower doses when used as monotherapy. Combinations of favipiravir and peramivir increased the numbers of survivors by 10-50% when the 0.025, 0.05, and 0.1mg/kg/d doses of peramivir were combined with 20mg/kg/d favipiravir and when all doses of peramivir were combined with 40mg/kg/d favipiravir. Three-dimensional analysis of drug interactions using the MacSynergy method indicates strong synergy for these drug combinations. In addition, an increase in lifespan for groups of mice treated with drug combinations, compared to the most effective monotherapy group, was observed for the 0.025, 0.05, and 0.1mg/kg/d doses of peramivir combined with favipiravir at the 20mg dose level. Therefore, the 20mg/kg/d dose of favipiravir was selected for further combination studies. Increased survival was exhibited when this dose was combined with peramivir doses of 0.1, 0.25 and 0.5mg/kg/d (1mg/kg/d of peramivir alone was 100% protective in this experiment). Improved body weight relative to either compound alone was evident using 0.25, 0.5, and 1mg/kg/d of peramivir. Significant reductions in lung hemorrhage score and lung weight were evident on day 6 post-infection. In addition, virus titers were reduced significantly on day 4 post-infection by combination therapy containing favipiravir combined with peramivir at 0.25 and 0.5mg/kg/d. These data demonstrate that combinations of favipiravir and peramivir perform better than suboptimal doses of each compound alone for the treatment of influenza virus infections in mice.
Copyright © 2012. Published by Elsevier B.V.
PMID:
22429564
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22429564
Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice.
Tarbet EB, Maekawa M, Furuta Y, Babu YS, Morrey JD, Smee DF.
Source
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, United States.
Abstract
Favipiravir, an influenza virus RNA polymerase inhibitor, and peramivir, an influenza virus neuraminidase inhibitor, were evaluated alone and in combination against pandemic influenza A/California/04/2009 (H1N1) virus infections in mice. Infected mice were treated twice daily for 5d starting 4h after virus challenge. Favipiravir was 40%, 70%, and 100% protective at 20, 40, and 100mg/kg/d. Peramivir was 30% protective at 0.5mg/kg/d, but ineffective at lower doses when used as monotherapy. Combinations of favipiravir and peramivir increased the numbers of survivors by 10-50% when the 0.025, 0.05, and 0.1mg/kg/d doses of peramivir were combined with 20mg/kg/d favipiravir and when all doses of peramivir were combined with 40mg/kg/d favipiravir. Three-dimensional analysis of drug interactions using the MacSynergy method indicates strong synergy for these drug combinations. In addition, an increase in lifespan for groups of mice treated with drug combinations, compared to the most effective monotherapy group, was observed for the 0.025, 0.05, and 0.1mg/kg/d doses of peramivir combined with favipiravir at the 20mg dose level. Therefore, the 20mg/kg/d dose of favipiravir was selected for further combination studies. Increased survival was exhibited when this dose was combined with peramivir doses of 0.1, 0.25 and 0.5mg/kg/d (1mg/kg/d of peramivir alone was 100% protective in this experiment). Improved body weight relative to either compound alone was evident using 0.25, 0.5, and 1mg/kg/d of peramivir. Significant reductions in lung hemorrhage score and lung weight were evident on day 6 post-infection. In addition, virus titers were reduced significantly on day 4 post-infection by combination therapy containing favipiravir combined with peramivir at 0.25 and 0.5mg/kg/d. These data demonstrate that combinations of favipiravir and peramivir perform better than suboptimal doses of each compound alone for the treatment of influenza virus infections in mice.
Copyright © 2012. Published by Elsevier B.V.
PMID:
22429564
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22429564