Anti-influenza A activity of combinations of amantadine and ribavirin in ferret tracheal ciliated epithelium.
The anti-influenza A activities of amantadine and ribavirin were investigated separately and in combination. Ferret tracheal ciliated epithelium was continuously exposed to the drugs at concentrations (0.25, 0.5, and 1 mg/l) comparable to those found in human serum after oral administration. Each drug alone produced a modest delay in A/Alaska/6/77 (H3N2) induced cytopathic effect. The combination of drugs synergistically delayed cytopathic effect. At 1 mg/l of each, cytopathic effect was prevented in 75% of rings for the 28-day duration of the experiment. This effect was greater than that of 32 mg/l of amantadine or 64 mg/l of ribavirin as single antiviral drugs. Peak virus production was suppressed 4.4 log-fold by the combination of 1 mg/l of each drug. This is in contrast to amantadine alone which suppressed peak virus production by 1 log-fold and ribavirin along which at 1 mg/l suppressed peak virus production by 1.9 log-fold. At lower concentrations, the drugs were at least additive in suppression of virus production.
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D002923:Cilia; D004357:Drug Synergism; D004848:Epithelium; D005289:Ferrets; D009980:Influenza A virus / Q000187:drug effects*; D012254:Ribavirin / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology*; D014132:Trachea; D014776:Virus Cultivation
D012263:Ribonucleosides; D012254:Ribavirin; D000547:Amantadine