Affiliation:
1. University of Virginia School of Medicine, Charlottesville 22908.
Abstract
Pirodavir (R77975) is a capsid-binding, antipicornaviral agent with in vitro activity against most rhinovirus (RV) serotypes. We conducted four double-blind, controlled trials to assess the efficacy of intranasal pirodavir in experimentally induced RV infection of susceptible volunteers. Intranasal pirodavir (2 mg per dose) or the hydroxypropyl-beta-cyclodextrin vehicle as a placebo was given by metered pump spray. In three prophylaxis trials, subjects were inoculated with RV within 10 min of the second and third doses. When sprays were given six times per day for a total of 25 doses, infection, detected by either virus shedding or seroconversion, developed in 100% of the 13 placebo-treated subjects and 58% of the 12 pirodavir-treated subjects (P = 0.015). Clinical colds developed in 54% of placebo-treated subjects and 8% of pirodavir-treated subjects during drug administration (efficacy = 85%, P = 0.03), although late-developing colds developed in several subjects in both groups. Significant reductions in morning symptom scores and in the frequency of abnormal middle-ear pressures were also found in the pirodavir group. In contrast, in two prophylaxis studies using three doses daily, no significant antiviral or clinical benefits were observed. When frequent sprays were initiated at 24 h after RV challenge, significant reductions in virus shedding but no clinical benefits were found. Intranasal pirodavir was generally well tolerated but was associated with an excess rate of transient unpleasant taste. The findings indicated that frequent intranasal sprays of pirodavir were effective in preventing experimentally induced RV illness.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
100 articles.
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