Table 3.
Comparison of oseltamivir (OS) and oseltamivir carboxylate (OC) concentrations when oseltamivir was administered alone (regimen B) or together with zanamivir (regimens C and D)a
| Drug and pharmacokinetic parameter | C:B |
D:B |
||
|---|---|---|---|---|
| Ratio (95% CI) | Bioequivalence CIb | Ratio (95% CI) | Bioequivalence CIb | |
| OC | ||||
| AUC0-12 | 0.969 (0.940−0.999) | 94.4–99.5 | 0.989 (0.960−1.020) | 96.4–101.5 |
| AUC0-∞ | 0.982 (0.932−1.035) | 93.8–102.8 | 0.977 (0.927−1.030) | 93.3–102.2 |
| Cmax | 1.005 (0.958−1.055) | 96.4–104.8 | 1.025 (0.977−1.075) | 98.3–106.8 |
| OS | ||||
| AUC0-12 | 0.996 (0.932−1.064) | 94.0–105.5 | 1.008 (0.943−1.078) | 95.2–106.8 |
| AUC0-∞ | 1.019 (0.952−1.090) | 96.0–108.0 | 1.022 (0.955−1.094) | 96.4–108.4 |
| Cmax | 0.938 (0.743−1.185) | 76.6–114.8 | 1.073 (0.850−1.355) | 87.7–131.3 |
AUC0-∞, area under the concentration-time curve extrapolated to infinity; AUC0-12, area under the concentration-time curve between 0 and 12 h; Cmax, maximum concentration. Pharmacokinetic parameters were estimated by noncompartmental analysis.
Bioequivalence CIs were calculated per FDA recommendations (7, 8): exp(Δ ± s√(2/n)t0.05,30, where Δ is the estimated difference in log-transformed values, s is the square root of the mean square error from the mixed-effect model, and t0.05,30 is the critical value of t distribution at α = 0.05 and degrees of freedom = 30. Equivalence is concluded when this CI lies within the 80 to 125% range.