TABLE 2.
Pulmonary virus titers 4 days after virus challenge of cotton rats administered ribavirin i.p. or by continuous spa dailya
| Expt no. and group | Challenge virus | Treatment | Daily doseb (mg/kg) | Route of inoculation | Virus titer (log10/g lung) in cotton rat no.:
|
Mean ± SD titer | |||
|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | ||||||
| Expt 1 | |||||||||
| 1 | MV | Placebo | 0 | spa | 4.6 | 4.6 | 4.1 | 4.6 | 4.5 ± 0.3 |
| 2 | MV | Ribavirin | 67 | spa | 4.6 | 4.6 | 3.6 | 4.1 | 4.2 ± 0.5 |
| 3 | RSV | Placebo | 0 | spa | 4.0 | 4.5 | 3.5 | 4.0 | 4.0 ± 0.4 |
| 4 | RSV | Ribavirin | 67 | spa | 2.0 | 0c | 3.0 | 2.5 | 2.3 ± 0.6d |
| Expt 2 | |||||||||
| 1 | MV | Placebo | 0 | i.p. | 4.5 | 4.0 | 4.0 | 4.5 | 4.3 ± 0.3 |
| 2 | MV | Ribavirin | 90 | i.p. | 3.5 | 3.5 | 4.0 | 4.0 | 3.8 ± 0.3 |
| 3 | MV | Ribavirin | 180 | i.p. | 3.0 | 4.0 | 3.5 | 3.5 | 3.5 ± 0.4 |
| 4 | MV | Ribavirin | 360 | i.p. | 3.5 | 3.5 | 3.0 | 3.5 | 3.1 ± 0.5d |
| Expt 3 | |||||||||
| 1 | RSV | Placebo | 0 | i.p. | 4.1 | 4.6 | 4.6 | 4.1 | 4.0 ± 0.4 |
| 2 | RSV | Ribavirin | 90 | i.p. | 3.5 | 3.5 | 2.5 | 2.6 | 3.0 ± 0.6d |
| 3 | RSV | Ribavirin | 180 | i.p. | 3.1 | 2.5 | 2.0 | 2.5 | 2.5 ± 0.5d |
Animals were inoculated i.n. on day 0 with 104 CCID50s of MV or RSV. On each of the next 3 days, the animals in experiment 1 were exposed for 16 h to continuous spas of placebo (distilled water) or ribavirin (reservoir concentration of 20 mg/ml), while those in experiments 2 and 3 were inoculated i.p. b.i.d. with either placebo (distilled water) or the indicated dose of ribavirin. All of the animals were killed on day 4 after virus inoculation, at which times their lungs were removed and tested for virus.
The daily dose for animals exposed to spa represents the estimated maximum dosage of ribavirin delivered per cotton rat. The calculation used to obtain this value is provided in Materials and Methods.
A titer of zero indicates that no virus was detected in the lung lavage sample. For statistical analyses, lungs without detectable virus were assigned a value of 1.5 (the minimal detectable level of virus in these assays was 2.0 log10/g of lung).
Boldfaced means and standard deviations indicate statistical significance between means (P ≤0.5) for these groups and the placebo controls as determined by the Mann-Whitney (experiments involving two groups) or Kruskal-Wallis (experiment 2) nonparametric analysis of variance test; the number of animals per group was 4.