Zanamivir, a potent inhibitor of
influenza A and B virus neuraminidases, is protective against experimental
human influenza when given intranasally twice daily. We conducted two studies to assess the pharmacokinetics and protective efficacy of a reduced frequency dosing regimen of topical
zanamivir. In the first study, 36 uninfected volunteers received a single dose of
zanamivir by intranasal spray (6.4 mg), intranasal drops (16 mg) or dry
powder oral inhalation (10 mg). At 4 h, median nasal wash concentrations were 50-fold higher after intranasal dosing than after inhalation. Substantial levels (spray group, median 4,596 ng/ml; drop group, 1,239 ng/ml) were detected in nasal wash 48 h after intranasal dosing. In the double-blinded efficacy study, 47 sero-susceptible volunteers were randomized to receive either placebo or
zanamivir intranasal spray (6.4 mg). Among the 43 subjects evaluated, decreases in viral shedding occurred in the group receiving one dose of
zanamivir 4 h prior to inoculation, whereas no significant benefit was observed in those receiving a single dose 48 h prior to challenge. In the group given three daily doses, reductions were seen in viral shedding and
infection. In the two regimens providing
zanamivir 4 h prior to inoculation, significant reductions in nasal mucus weight were observed. Decreases in total symptom scores and the incidence of upper respiratory illness also occurred, but they did not reach statistical significance. The efficacy of a single dose of
zanamivir given 4 h prior to inoculation supports the hypothesis that influenza virus
neuraminidase is essential for initial virus spread through respiratory secretions. These findings indicate that once daily dosing of
zanamivir is protective against experimental
influenza A
infection.