Giuseppe
Emeritus
Antimicrob Agents Chemother. 2009 Jul 20. [Epub ahead of print]
Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro.
Nguyen JT, Hoopes JD, Smee DF, Prichard MN, Driebe EM, Engelthaler DM, Le MH, Keim PS, Spence RP, Went GT. Adamas Pharmaceuticals, Inc., Emeryville, California; Institute for Antiviral Research, Utah State University, Logan, Utah; University of Alabama School of Medicine, Birmingham, Alabama; Translational Genomics Research Institute, Flagstaff, Arizona.
The recurring emergence of influenza strains resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza pandemic. Currently, virtually all circulating strains of influenza A in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will address the issue of recurring resistance should be developed. We have tested double and triple combinations of the approved anti-influenza drugs, oseltamivir and amantadine, together with ribavirin against three influenza virus strains using cytopathic effect inhibition assays in MDCK cells. We selected A/New Caledonia/20/99 (H1N1) and A/Sydney/05/97 (H3N2) as representatives of the wildtype versions of the predominant circulating seasonal influenza strains, and A/Duck/MN1525/81 (H5N1) as a representative of avian influenza strains. Dose response curves were generated for all drug combinations, and the degree of drug interaction was quantified using a model that calculates the synergy (or antagonism) between the drugs in double and triple combinations. This report demonstrates that a triple combination of antivirals was highly synergistic against influenza A. Importantly, the synergy of the triple combination was 2- to 13-fold greater than the synergy of any double combination, depending on the influenza subtype. These data support the investigation of a novel combination of oseltamivir, amantadine, and ribavirin as an effective treatment for both seasonal and pandemic influenza, allowing efficient use of the existing drug supplies.
PMID: 19620324 [PubMed - as supplied by publishe
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Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro.
Nguyen JT, Hoopes JD, Smee DF, Prichard MN, Driebe EM, Engelthaler DM, Le MH, Keim PS, Spence RP, Went GT. Adamas Pharmaceuticals, Inc., Emeryville, California; Institute for Antiviral Research, Utah State University, Logan, Utah; University of Alabama School of Medicine, Birmingham, Alabama; Translational Genomics Research Institute, Flagstaff, Arizona.
The recurring emergence of influenza strains resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza pandemic. Currently, virtually all circulating strains of influenza A in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will address the issue of recurring resistance should be developed. We have tested double and triple combinations of the approved anti-influenza drugs, oseltamivir and amantadine, together with ribavirin against three influenza virus strains using cytopathic effect inhibition assays in MDCK cells. We selected A/New Caledonia/20/99 (H1N1) and A/Sydney/05/97 (H3N2) as representatives of the wildtype versions of the predominant circulating seasonal influenza strains, and A/Duck/MN1525/81 (H5N1) as a representative of avian influenza strains. Dose response curves were generated for all drug combinations, and the degree of drug interaction was quantified using a model that calculates the synergy (or antagonism) between the drugs in double and triple combinations. This report demonstrates that a triple combination of antivirals was highly synergistic against influenza A. Importantly, the synergy of the triple combination was 2- to 13-fold greater than the synergy of any double combination, depending on the influenza subtype. These data support the investigation of a novel combination of oseltamivir, amantadine, and ribavirin as an effective treatment for both seasonal and pandemic influenza, allowing efficient use of the existing drug supplies.
PMID: 19620324 [PubMed - as supplied by publishe
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