TABLE 2.
Effect of combinations of amantadine, oseltamivir carboxylate, and ribavirin on an influenza A/Duck/MN/1525/81 (H5N1) amantadine-resistant virus infection in MDCK cells
| Drug | Concn (μM) | Virus titers with:a
|
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amantadine (μM)
|
Ribavirin (μM)
|
||||||||||||
| 100 | 32 | 10 | 3.2 | 1 | 0 | 100 | 32 | 10 | 3.2 | 1.0 | 0 | ||
| Oseltamivir carboxylate | 10 | 0 ± 0 | 0.7 ± 1.2 | 0.6 ± 1.0 | 0.7 ± 1.2 | 0.6 ± 1.0 | 0.7 ± 1.2 | 0 ± 0 | 0 ± 0 | 0.6 ± 1.0 | 0.5 ± 0.9 | 0.4 ± 0.8 | 0.7 ± 1.2 |
| 3.2 | 1.6 ± 1.5 | 1.8 ± 0.7 | 1.5 ± 1.4 | 1.8 ± 1.7 | 1.4 ± 1.4 | 1.6 ± 1.5 | 0 ± 0 | 0 ± 0 | 1.3 ± 1.2 | 1.7 ± 1.5 | 1.7 ± 1.5 | 1.5 ± 1.5 | |
| 1.0 | 4.1 ± 0.5 | 4.5 ± 0.5 | 4.3 ± 0.8 | 4.6 ± 0.7 | 3.9 ± 0.8 | 4.2 ± 0.5 | 0 ± 0 | 0.2 ± 0.4 | 3.7 ± 0.3 | 4.3 ± 0.0 | 4.4 ± 0.1 | 4.6 ± 0.5 | |
| 0.32 | 5.2 ± 0.8 | 5.4 ± 0.2 | 5.3 ± 0.4 | 5.4 ± 0.6 | 5.2 ± 0.6 | 4.7 ± 0.9 | 0 ± 0 | 1.2 ± 1.0 | 4.6 ± 0.9 | 4.9 ± 0.9 | 5.2 ± 0.8 | 5.1 ± 0.5 | |
| 0.1 | 5.3 ± 0.8 | 5.5 ± 0.0 | 5.7 ± 0.4 | 5.7 ± 0.3 | 5.6 ± 0.1 | 5.0 ± 0.9 | 0 ± 0 | 2.1 ± 1.9 | 4.9 ± 0.7 | 5.0 ± 0.9 | 5.4 ± 0.6 | 5.5 ± 0.3 | |
| 0 | 5.6 ± 0.3 | 5.8 ± 0.2 | 5.7 ± 0.3 | 5.6 ± 0.4 | 5.6 ± 0.4 | 5.5 ± 0.5 | 0 ± 0 | 2.5 ± 2.2 | 5.4 ± 0.5 | 5.2 ± 0.5 | 5.5 ± 0.2 | 5.6 ± 0.4 | |
| Amantadine | 100 | 0 ± 0 | 1.6 ± 1.7 | 4.5 ± 0.5 | 5.1 ± 0.5 | 5.5 ± 0.9 | 5.5 ± 0.2 | ||||||
| 32 | 0 ± 0 | 2.0 ± 1.8 | 4.9 ± 0.3 | 5.5 ± 0.2 | 5.5 ± 0.2 | 5.9 ± 0.1 | |||||||
| 10 | 0 ± 0 | 2.3 ± 2.0 | 4.9 ± 0.4 | 5.5 ± 0.4 | 5.5 ± 0.2 | 5.8 ± 0.1 | |||||||
| 3.2 | 0 ± 0 | 2.1 ± 1.9 | 4.7 ± 0.0 | 5.3 ± 0.5 | 5.3 ± 0.5 | 5.6 ± 0.4 | |||||||
| 1 | 0 ± 0 | 2.1 ± 1.9 | 4.7 ± 0.3 | 5.2 ± 0.5 | 5.4 ± 0.2 | 5.6 ± 0.4 | |||||||
| 0 | 0 ± 0 | 2.6 ± 2.3 | 4.8 ± 0.3 | 5.4 ± 0.1 | 5.5 ± 0.1 | 5.6 ± 0.1 | |||||||
a
The values are means ± standard deviations (n = 3 independent assays) of virus titers (log10 CCID50/0.1 ml). The volume of synergy value, as calculated by the method of Prichard and Shipman (23), was 1.81 for oseltamivir carboxylate and amantadine, 3.95 for oseltamivir carboxylate and ribavirin, and 5.74 for amantadine and ribavirin. Boldface values indicate regions of synergy.