Giuseppe
Emeritus
Antimicrob Agents Chemother. 2009 Mar 9. [Epub ahead of print]
Effects of Double Combinations of Amantadine, Oseltamivir, and Ribavirin on Influenza A (H5N1) Virus Infections in Cell Culture and in Mice.
Smee DF, Hurst BL, Wong MH, Bailey KW, Morrey JD. - Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah.
An amantadine-resistant influenza A/Duck/MN/1525/81 (H5N1) virus was developed from the low pathogenic North American wild-type (amantadine-sensitive) virus for studying treatment of infections in cell culture and in mice.
Double combinations of amantadine, oseltamivir (or the cell culture-active form, oseltamivir carboxylate), and ribavirin were used.
Amantadine-oseltamivir carboxylate and amantadine-ribavirin combinations showed synergistic interactions over a range of doses against wild-type virus in Madin-Darby canine kidney (MDCK) cell culture, but not oseltamivir carboxylate-ribavirin combinations.
Primarily additive interactions were seen with oseltamivir carboxylate-ribavirin combinations against amantadine-resistant virus.
The presence of amantadine in drug combinations against the resistant virus did not improve activity.
The wild-type and amantadine-resistant viruses were lethal to mice by intranasal instillation.
The resistant virus infection could not be treated with amantadine up to 100 mg/kg/day, whereas the wild-type virus infection was treatable with oral doses of 10 (weakly effective) to 100 mg/kg/day administered twice a day for 5 days starting 4 h prior to virus exposure.
Drug combination studies showed that treatment of the amantadine-resistant virus infection with amantadine-oseltamivir or amantadine-ribavirin combinations were not significantly better than using oseltamivir or ribavirin alone.
In contrast, the oseltamivir-ribavirin (25 and 75 mg/kg/day combinations) treatments produced significant reductions in mortality.
The wild-type virus infection was markedly reduced in severity by all three combinations (amantadine, 10 mg/kg/day combined with the other compounds at 20 or 40 mg/kg/day) compared to monotherapy with the three compounds.
Results indicate lack of benefit of amantadine in combinations against amantadine-resistant virus, but positive benefits in combinations against amantadine-sensitive virus.
PMID: 19273672 [PubMed - as supplied by publisher]
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Effects of Double Combinations of Amantadine, Oseltamivir, and Ribavirin on Influenza A (H5N1) Virus Infections in Cell Culture and in Mice.
Smee DF, Hurst BL, Wong MH, Bailey KW, Morrey JD. - Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah.
An amantadine-resistant influenza A/Duck/MN/1525/81 (H5N1) virus was developed from the low pathogenic North American wild-type (amantadine-sensitive) virus for studying treatment of infections in cell culture and in mice.
Double combinations of amantadine, oseltamivir (or the cell culture-active form, oseltamivir carboxylate), and ribavirin were used.
Amantadine-oseltamivir carboxylate and amantadine-ribavirin combinations showed synergistic interactions over a range of doses against wild-type virus in Madin-Darby canine kidney (MDCK) cell culture, but not oseltamivir carboxylate-ribavirin combinations.
Primarily additive interactions were seen with oseltamivir carboxylate-ribavirin combinations against amantadine-resistant virus.
The presence of amantadine in drug combinations against the resistant virus did not improve activity.
The wild-type and amantadine-resistant viruses were lethal to mice by intranasal instillation.
The resistant virus infection could not be treated with amantadine up to 100 mg/kg/day, whereas the wild-type virus infection was treatable with oral doses of 10 (weakly effective) to 100 mg/kg/day administered twice a day for 5 days starting 4 h prior to virus exposure.
Drug combination studies showed that treatment of the amantadine-resistant virus infection with amantadine-oseltamivir or amantadine-ribavirin combinations were not significantly better than using oseltamivir or ribavirin alone.
In contrast, the oseltamivir-ribavirin (25 and 75 mg/kg/day combinations) treatments produced significant reductions in mortality.
The wild-type virus infection was markedly reduced in severity by all three combinations (amantadine, 10 mg/kg/day combined with the other compounds at 20 or 40 mg/kg/day) compared to monotherapy with the three compounds.
Results indicate lack of benefit of amantadine in combinations against amantadine-resistant virus, but positive benefits in combinations against amantadine-sensitive virus.
PMID: 19273672 [PubMed - as supplied by publisher]
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