Treatment of Influenza Infection of Mice by Using Rimantadine Hydrochlorides by the Aerosol and Intraperitoneal Routes

Abstract

Rimantadine hydrochloride was administered for 4 days in a small-particle (95% < 6.5 μm) aerosol (8.8 mg/kg per day) or intraperitoneally (40 mg/kg per day) to mice previously infected with influenza A/Aichi/2/68 (H 3 N 2 ), mouse adapted. Mean time to death and incidence of survival were significantly increased in all treated groups of mice. The rate of eventual disappearance of virus from lung tissue was also accelerated by therapy. However, maximal mean virus titer per lung, and lung histopathology, did not reveal any difference between control and either group of treated mice. Aerosol therapy initiated at 72 h postinfection was as effective as that initiated at 6 h, even though lung virus titers of these mice had already peaked by 72 h. In contrast, intraperitoneal therapy initiated at 72 h was not effective in all studies.

Therapeutic Effects of Small-Particle Aerosols of Ribavirin on Parainfluenza (Sendai) Virus Infections of Mice

“…Therapeutic efficacy was demonstrated by increased survival rates, extended times to death, later development of gross lung pathology, and reduction of pulmonary virus concentrations. The effects of ribavirin were similar to those observed in the treatment of type A influenza virus infections (8,12). Our results suggest that the lung and not the upper respiratory tract may be the important tissue in determining the outcome of Sendai infections in mice.…”

“…In recent work, ribavirin was highly effective for the treatment of influenza type A infections in animals when administered therapeutically as small-particle aerosols (SPAs) (8,9,12). This report describes the therapeutic efficacy of ribavirin given as a SPA to mice infected with a lethal respiratory dose of Sendai virus.…”

“…The methods used for challenging mice with infectious virus and the procedures for continuous aerosol therapy have been described previously (8,9). In the ribavirin studies, the concentration of drug in the spray suspension was adjusted to yield an effective, retained aerosol dose of 50 mg of ribavirin per kg (mouse weight) per day or 100 mg/kg in 48 h of treatment.…”

“…The Sendai virus concentrations in lung, tracheobronchial and nasopharyngeal tissues were determined for each mouse and the extent of lung consolidation was scored. The methods used to quantitate virus concentrations in mouse respiratory tissues have been described (8). Virus assays were performed in embryonated chicken eggs; tissue virus levels were measured in terms of median egg infectious doses/whole tissue.…”

Activity of Amantadine, Rimantadine, and Ribavirin Against Swine Influenza in Mice and Squirrel Monkeys

“…Amantadine, rmantadine, and ribavirin have demonstrated activity against disease caused by several strains of type A influenza virus (6,8,9,12,13). This paper reports results of studies on the efficacy of these three drugs given by the oral route for the prevention and/or treatment of type A/New Jersey (swine) influenza virus infections in mice.…”