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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, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, John D. Morrey
Effects Of Double Combinations Of Amantadine, Oseltamivir, And Ribavirin On Influenza A (H5n1) Virus Infections In Cell Culture And In Mice, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, John D. Morrey
John D. Morrey
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 oseltamivir carboxylate-ribavirin combinations did not. 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 …