Amantadine aerosols in normal volunteers: pharmacology and safety testing

The acceptability and pharmacology of intermittent aerosol administration of amantadine was assessed in healthy volunteers. Amantadine solutions of 2.5, 1.5, or 1.0 g/100 ml were used for 12 30-min, twice-daily aerosol treatments in 15 subjects. Overall, the aerosol treatments were well tolerated. During and up to 1 h after aerosol exposures, nasal irritation, rhinorrhea, dysgeusia, or a combination of symptoms was experienced by some of the subjects receiving either of the two higher amantadine concentrations. Aerosol treatments were associated with small but statistically significant decreases in maximal expiratory flow rates. One hour after aerosol treatments with the 1.0-g/100 ml solution, amantadine levels in nasal wash samples (mean, 30.3 micrograms/ml; range, 1.7 to 108 micrograms/ml) greatly exceeded blood and nasal wash levels reported after oral administration. Amantadine can be administered safely by small-particle aerosol to humans in doses that could be expected to exert an antiviral effect in influenza A virus infections.