TABLE 3.
Effect of four-times-daily treatmenta with T-705 or oseltamivir on an infection in mice induced by influenza A/Duck/MN/1525/81 (H5N1) virus
| Expt no. and treatmenta | Dose (mg/kg/day) | Infected, treated miceg
|
Toxicity controls
|
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. of survivors/total no. tested | MDDb ± SD | Day 1 mean lung virus titerc ± SD | Day 6 mean lung scored ± SD | Day 6 mean lung wt (mg) ± SD | Mean day 11 SaO2 (%) ± SD | No. of survivors/total no. tested following rechallengee | No. of survivors/total no. tested | Mean host wt changef (g) | ||
| Expt 1 | ||||||||||
| T-705 | 300 | 10/10*** | >21.0*** | 3.5 ± 0.8*** | 0.3 ± 0.3* | 146 ± 12*** | 88.6 ± 3.8*** | 10/10 | 3/3 | 0.6 |
| T-705 | 100 | 10/10*** | >21.0*** | 4.9 ± 0.3** | 0.5 ± 0.0* | 140 ± 20*** | 85.9 ± 5.9*** | 10/10 | 3/3 | 1.1 |
| T-705 | 33 | 10/10*** | >21.0*** | 5.8 ± 0.5 | 1.3 ± 0.3* | 217 ± 6** | 84.8 ± 4.8*** | 10/10 | 3/3 | 0.2 |
| Oseltamivir | 20 | 2/10 | 9.4 ± 1.2*** | 6.1 ± 0.5 | 2.2 ± 0.6* | 270 ± 36* | 76.9 ± 3.8* | 0/2 | 3/3 | 0.6 |
| CMC | 0/20 | 6.6 ± 1.1 | 6.3 ± 0.4 | 3.3 ± 0.3 | 360 ± 42 | 75.0 ± 0.0 | ||||
| Healthy controls | 0.0 ± 0.0 | 0.0 ± 0.0 | 117 ± 21 | 92.6 ± 3.5 | 0/5 | 3/3 | 0.8 | |||
| Expt 2 | ||||||||||
| T-705 | 300 | 9/9*** | >21.0*** | 2.4 ± 0.4*** | 0.5 ± 0.0* | 123 ± 15*** | 85.9 ± 6.9*** | 9/9 | 3/3 | 0.0 |
| T-705 | 100 | 10/10*** | >21.0*** | 5.3 ± 0.3** | 0.7 ± 0.3* | 153 ± 15*** | 84.6 ± 4.4*** | 10/10 | 3/3 | −0.1 |
| T-705 | 33 | 9/10*** | 12.0 ± 0.0 | 5.8 ± 0.4 | 1.7 ± 0.6* | 173 ± 6*** | 81.6 ± 6.3*** | 9/9 | 3/3 | 0.0 |
| Oseltamivir | 20 | 1/10 | 9.3 ± 1.7*** | 6.3 ± 0.1 | 3.5 ± 0.0 | 247 ± 23** | 76.6 ± 3.9 | 1/1 | 3/3 | 0.2 |
| CMC | 0/20 | 6.1 ± 0.8 | 6.4 ± 0.4 | 3.6 ± 0.2 | 328 ± 13 | 75.0 ± 0.0 | ||||
| Healthy controls | 5/5 | >21.0 | 0.0 ± 0.0 | 0.0 ± 0.0 | 117 ± 6 | 93.2 ± 2.8 | 0/5 | 3/3 | 1.3 | |
The doses were administered every 6 h for 5 days beginning 1 h after virus exposure (oseltamivir was given twice daily for 5 days beginning 1 h after virus exposure).
MDD, mean day to death of mice dying prior to day 21.
Log10 CCID50/g.
Plum coloration of lung ranging from 0 (normal lung) to 4 (maximal coloration).
Rechallenged with 100-fold more virus on day 21.
Difference between initial weight and weight 18 h after final treatment.
*, P < 0.05 compared to the results for the CMC-treated controls; **, P < 0.01 compared to the results for the CMC-treated controls; ***, P < 0.001 compared to the results for the CMC-treated controls.