MegaRibavirin aerosol for the treatment of influenza A virus infections in mice.

While newer neuraminidase inhibitors have been used recently to treat influenza A and B virus infections, emergence of drug resistance poses potential problems. Previous ribavirin aerosol treatments of influenza were effective and drug resistance was not observed. To make ribavirin aerosol treatment a quicker process and limited to once or twice daily treatments, a MegaRibavirin formulation (100 mg of ribavirin/mL) was developed that when used with the Aerotech II nebulizer was effective in preventing death in a lethal influenza A virus mouse model. Aerosol generated using the Aerotech II nebulizer flowing at 10 L of air/min produced aerosol droplets that contained 2.3 mg of ribavirin/L with a mass median aerodynamic diameter of 1.8 microm. Using this system for treatment, a single daily 30-min exposure on days 1-4 produced a survival rate of greater than 90%. Delaying the start of aerosol treatment for 48 or 72 h and treating once daily for 30 min for two days (days 2-3 and 3-4, respectively) still significantly increased the number of survivors and mean time to death. For the treatment of influenza in general and for pandemic avian influenza, the MegaRibavirin-Aerotech II method of aerosol treatment allows for short treatment periods, minimizes environmental issues and costs less.