Table 2. The 50% effective concentration (EC50) of amantadine, ribavirin, and oseltamivir carboxylate as single agents and in double and triple combinations against 2009 H1N1 A/California/10/09 (CA10) as determined by Neutral Red assay.
Test Article | EC50 (µg/mL) | 95% Confidence interval | Fold Reduction in EC50 Compared to (A) | Fold Reduction in EC50 Compared to (B) | Fold Reduction in EC50 Compared to (C) | P-values Compared to (A) | P-values Compared to (B) | P-values Compared to (C) |
Amantadine | ||||||||
(A) alone | 24 | 23–25 | – | – | – | – | – | – |
(B) with 1 µg/mL ribavirin | 13 | 12–14 | 1.8 | – | – | <0.0001 | – | – |
(C) with 0.0032 µg/mL oseltamivir carboxylate | 12 | 11–14 | 2.0 | – | – | <0.0001 | – | – |
(D) with 1 µg/mL ribavirin and 0.0032 µg/mL oseltamivir carboxylate | 7.6 | 6.0–9.6 | 3.2 | 1.7 | 1.6 | <0.0001 | <0.0001 | <0.0001 |
Ribavirin | ||||||||
(A) alone | 6.5 | 6.2–6.9 | – | – | – | – | – | – |
(B) with 0.0032 µg/mL oseltamivir carboxylate | 3.5 | 3.2–3.9 | 1.9 | – | – | <0.0001 | – | – |
(C) with 1 µg/mL amantadine | 5.2 | 4.6–5.9 | 1.2 | – | – | 0.007 | – | – |
(D) with 0.0032 µg/mL oseltamivir carboxylate and 1 µg/mL amantadine | 2.4 | 1.7–3.4 | 2.7 | 1.5 | 2.2 | <0.0001 | 0.0143 | <0.0001 |
Oseltamivir carboxylate | ||||||||
(A) alone | 0.055 | 0.037–0.081 | – | – | – | – | – | – |
(B) with 1 µg/mL ribavirin | 0.022 | 0.015–0.032 | 2.5 | – | – | 0.0009 | – | – |
(C) with 1 µg/mL amantadine | 0.022 | 0.012–0.037 | 2.5 | – | – | 0.003 | – | – |
(D) with 1 µg/mL ribavirin and 1 µg/mL amantadine | 0.0034 | 0.0009–0.012 | 16.2 | 6.5 | 6.5 | <0.0001 | 0.0437 | 0.0015 |
EC50 values are the mean of five experiments (three replicates per experiment).