Table 3.
Summary of mean pharmacokinetic parameters and oral bioavailability of EMA200, EMA300, EMA400, and EMA401 (S-enantiomer of EMA400) in adult male SD rats (adapted from Smith and colleagues103 with permission).
| Parameter | EMA200 | EMA300 (sodium salt) | EMA400 | EMA401 (sodium salt) |
|---|---|---|---|---|
| t½ (h) | 3.6 | 8.2 | 5.9 | 2.3 |
| Vd (L/kg) | 47.3 | 76.8 | 6.0 | 3.7 |
| Cl (L/h/kg) | 9.3 | 6.1 | 0.71 | 1.1 |
| Oral Tmax (h) | 0.23 | 0.36 | 0.33 | 2.0 |
| Dose-normalized oral Cmax (kg/mL) | 7.3 | 6.8 | 130.4 | 88.5 |
| Dose-normalized oral AUC0-∞ (hour.kg/mL) | 6.5* | 13.9 | 398.6 | 301 |
| F (%) | 5.9 | 7.1 | 28 | 33.2 |
AUC0-∞ = area under the plasma concentration vs time curve from time zero extrapolated to infinity; Cl = systemic clearance; Cmax = peak plasma concentration after oral dosing; F (%) = oral bioavailability; t½ = terminal elimination half-life; Tmax = time of Cmax after oral dosing; Vd = volume of distribution; *value based on AUC0-t, where t is the last measurable plasma concentration.