Comparative therapeutic effect of aerosolized and oral rimantadine HC1 in experimental human influenza A virus infection

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Thirty-six adult volunteers were inoculated intranasally with 7.2 log10 egg infectious doses 50% of an attenuated A/Khabarovsk/77/H1N1 virus. Twenty-four hours later volunteers were begun on both aerosol treatments (rimantadine HCl 25 mg in saline or saline, 10 min exposure twice daily) and oral medications (rimantadine HCl 50 mg or placebo every 6 h, three times daily) which were administered for 5 days. Virus-positive volunteers receiving placebo by both of the two routes had a peak in clinical illness scores on the second treatment day (mean score 5.3), which was not observed in either the aerosol rimantadine (0.6) or oral rimantadine (0.9) treated volunteers. On the second treatment day, the proportion of virus-positive volunteers with elevated axillary temperature measurements and the mean peak temperature measurement were also significantly reduced in both drug groups. No significant effects on the duration of virus shedding were noted. In experimental influenza A virus infection, characterized by mild clinical illness and short duration of virus shedding, low doses of aerosolized rimantadine had a therapeutic effect comparable to that found with larger doses of oral rimantadine.