Giuseppe
Emeritus
Antimicrob Agents Chemother. 2009 Nov 9. [Epub ahead of print]
Effects of Combinations of Favipiravir (T-705) and Oseltamivir on Influenza A (H1N1, H3N2, and H5N1) Virus Infections in Mice.
Smee DF, Hurst BL, Wong MH, Bailey KW, Tarbet EB, Morrey JD, Furuta Y. - Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah; Toyama Chemical Co. Ltd., Tokyo, Japan.
Favipiravir (T-705, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and oseltamivir were combined to treat influenza A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), and A/Duck/MN/1525/81 (H5N1) virus infections. T-705 alone inhibited viruses in cell culture at 1.4-4.3 muM. Oseltamivir inhibited these three viruses in cells at 3.7, 0.02, and 0.16 muM, and at 0.94, 0.46, and 2.31 nM in neuraminidase assays, respectively. Oral treatments were given twice daily to mice for 5-7 days starting generally 24 h after infection. Survival resulting from 5 days of oseltamivir treatment (0.1 and 0.3 mg/kg/day) was significantly better in combination with 20 mg/kg/day of T-705 against the H1N1 infection. Treatment of the H3N2 infection required 50 mg/kg/day of oseltamivir for 7 days to achieve 60% protection; 25 mg/kg/day was ineffective. T-705 was >=70% protective at 50-100 mg/kg/day but inactive at 25 mg/kg/day. Combination of inhibitors (25 mg/kg/day each) increased survival to 90%. The H5N1 infection was not benefited by treatment with oseltamivir (<=100 mg/kg/day for 7 days). T-705 was 30-70% protective at 25-100 mg/kg/day. Survival improved slightly for combination treatments. Increased activity was seen against H5N1 infection by starting treatments 2 h before infection. Oseltamivir was ineffective at <=40 mg/kg/day. T-705 was 100% protective at 40 and 80 mg/kg/day and inactive at 20 mg/kg/day. Combining ineffective doses (20 mg/kg/day T-705 and 10-40 mg/kg/day of oseltamivir) afforded 60-80% protection, and improved body weights during infection. Thus, synergistic responses were achieved with low doses of T-705 combined with oseltamivir. These compounds may be viable candidates for combination treatment of human influenza infections.
PMID: 19901093 [PubMed - as supplied by publisher]
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http://www.ncbi.nlm.nih.gov/sites/entrez
Effects of Combinations of Favipiravir (T-705) and Oseltamivir on Influenza A (H1N1, H3N2, and H5N1) Virus Infections in Mice.
Smee DF, Hurst BL, Wong MH, Bailey KW, Tarbet EB, Morrey JD, Furuta Y. - Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah; Toyama Chemical Co. Ltd., Tokyo, Japan.
Favipiravir (T-705, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and oseltamivir were combined to treat influenza A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), and A/Duck/MN/1525/81 (H5N1) virus infections. T-705 alone inhibited viruses in cell culture at 1.4-4.3 muM. Oseltamivir inhibited these three viruses in cells at 3.7, 0.02, and 0.16 muM, and at 0.94, 0.46, and 2.31 nM in neuraminidase assays, respectively. Oral treatments were given twice daily to mice for 5-7 days starting generally 24 h after infection. Survival resulting from 5 days of oseltamivir treatment (0.1 and 0.3 mg/kg/day) was significantly better in combination with 20 mg/kg/day of T-705 against the H1N1 infection. Treatment of the H3N2 infection required 50 mg/kg/day of oseltamivir for 7 days to achieve 60% protection; 25 mg/kg/day was ineffective. T-705 was >=70% protective at 50-100 mg/kg/day but inactive at 25 mg/kg/day. Combination of inhibitors (25 mg/kg/day each) increased survival to 90%. The H5N1 infection was not benefited by treatment with oseltamivir (<=100 mg/kg/day for 7 days). T-705 was 30-70% protective at 25-100 mg/kg/day. Survival improved slightly for combination treatments. Increased activity was seen against H5N1 infection by starting treatments 2 h before infection. Oseltamivir was ineffective at <=40 mg/kg/day. T-705 was 100% protective at 40 and 80 mg/kg/day and inactive at 20 mg/kg/day. Combining ineffective doses (20 mg/kg/day T-705 and 10-40 mg/kg/day of oseltamivir) afforded 60-80% protection, and improved body weights during infection. Thus, synergistic responses were achieved with low doses of T-705 combined with oseltamivir. These compounds may be viable candidates for combination treatment of human influenza infections.
PMID: 19901093 [PubMed - as supplied by publisher]
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http://www.ncbi.nlm.nih.gov/sites/entrez
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