Efficacy of high dose-short duration ribavirin aerosol in the treatment of respiratory syncytial virus infected cotton rats and influenza B virus infected mice.

Fifteen to 20 mg/ml ribavirin administered as a small particle aerosol for 10-18 h per day is currently the regimen generally used to treat experimental or naturally-occurring respiratory syncytial (RS) or influenza virus infections in humans. To determine if such prolonged treatment schedules could be reduced, cotton rats and mice were inoculated with RS or influenza B virus, respectively, and then treated with different concentrations of ribavirin small particle aerosols. Aerosols generated from reservoirs containing 60 mg/ml ribavirin given 2 h twice daily, protected cotton rats from RS virus and mice from influenza B virus as well as aerosols generated from reservoirs containing 20 mg/ml ribavirin given 11 h daily. Aerosols generated from reservoirs containing 40 or 20 mg/ml given 2 h daily were less efficacious. There was no evidence of intolerance or pulmonary histopathology in infected or uninfected animals exposed to any of the doses of ribavirin tested. These studies indicate that use of aerosols containing higher concentrations of ribavirin than generally used to treat respiratory virus diseases may permit significantly shorter treatment schedules without loss of efficacy or increase in toxicity.