Small-Particle Aerosols of Antiviral Compounds in Treatment of Type A Influenza Pneumonia in Mice

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Abstract
Three chemotherapeutic drugs active against type A influenza virus (amantadine, rimantadine, and ribavirin) were tested as therapeutic agents against established infections with influenza virus in mice. The drugs were administered intraperitoneally or as aerosols either from 6 hr to four days or from three to seven days after infection. Small-particle aerosols were administered continuously 24 hr per day. Continuous dissemination of aerosols was superior to intraperitoneal administration, as evidenced by higher survival rates at 21 days. Rimantadine, amantadine, and ribavirin were effective when treatment was delayed for three days. Ribavirin was the most efficacious if therapy was initiated as an aerosol 6 hr after infection. In contrast to amantadine, ribavirin given in small-particle aerosols at 6 hr prevented the development of pneumonia and decreased titers of virus in lung.

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