title: Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection.
abstract: Zanamivir is a potent inhibitor of influenza A and B virus neuraminidases and is active topically in experimental and natural human influenza. We conducted this double-blinded, placebo-controlled study to evaluate the safety and efficacy of intravenously administered zanamivir. Susceptible volunteers were randomized to receive either saline or zanamivir (600 mg) intravenously twice daily for 5 days beginning 4 h prior to intranasal inoculation with approximately 10(5) 50% tissue culture infectious doses (TCID50) of influenza A/Texas/36/91 (H1N1) virus. Reductions in the frequency of viral shedding (0% versus 100% in placebo, P < 0.005) and seroconversion (14% versus 100% in placebo, P < 0.005) and decreases in viral titer areas under the curve (0 versus 11.6 [median] log10 TCID50. day/ml in placebo, P < 0.005) were observed in the zanamivir group, as were reductions in fever (14% versus 88% in placebo, P < 0.05), upper respiratory tract illness (0% versus 100% in placebo, P < 0.005), total symptom scores (1 versus 44 [median] in placebo, P < 0.005), and nasal-discharge weight (3.9 g versus 17.5 g [median] in placebo, P < 0.005). Zanamivir was detectable in nasal lavage samples collected on days 2 and 4 (unadjusted median concentrations, 10.5 and 12.0 ng/ml of nasal wash, respectively). This study demonstrates that intravenously administered zanamivir is distributed to the respiratory mucosa and is protective against infection and illness following experimental human influenza A virus inoculation.
authors.affiliation: Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Calfee
authors.forename: A W
authors.initials: AW
authors.lastname: Peng
authors.forename: L M
authors.initials: LM
authors.lastname: Cass
authors.forename: M
authors.initials: M
authors.lastname: Lobo
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D006146:Guanidines; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011714:Pyrans; D012794:Sialic Acids / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D053243:Zanamivir
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir