Table 7. Rat Plasma Pharmacokinetic Parameters after Intravenous (IV) or Oral (PO) Administrationa.
| intravenous administration | ||||||
|---|---|---|---|---|---|---|
| parameter | 1b | 35 | 11 | 13 | 7 | 9 |
| dose (mg/kg) | 2.6 | 1.8 | 2.0 | 1.1 | 1.9 | 1.6 |
| rat PPB (% bound) | 97.7 | 94.2 | 99.7 | 97.2 | 99.2 | 96.4 |
| blood/plasma | 0.8 | 1.2 | 0.7 | 1.5 | 0.7 | 1.5 |
| apparent T1/2 (h) | 12.6 | 11.2 | 6.2 | 6.1 | 7.1 | 5.9 |
| AUC0-inf (μM·h) | 17.4 (0.40) | 27.1 (1.57) | 30 (0.09) | 2.0 (0.05) | 24 (0.19) | 3.5 (0.12) |
| CLp (mL/min/kg) | 6.0 (263) | 3.0 (52) | 2.8 (933) | 22.4 (800) | 3.5 (438) | 21.2 (589) |
| Vss (L/kg) | 5.9 (257) | 2.7 (47) | 1.1 (367) | 8.7 (311) | 1.5 (188) | 6.7 (186) |
| oral administration | ||||||
|---|---|---|---|---|---|---|
| parameter | 1b | 35 | 11 | 13 | 7 | 9 |
| dose (mg/kg) | 18.8 | 21.3 | 24.4 | 18.3 | 18.2 | 17.5 |
| Tmax (h) | 7.0 | 4.0 | 2.5 | 3.3 | 4.0 | 3.3 |
| Cmax (μM) | 3.9 (0.09) | 12.5 (0.72) | 37 (0.11) | 2.7 (0.07) | 23.8 (0.19) | 3.3 (0.12) |
| AUC0-inf (μM·h) | 122 (2.80) | 202 (11.7) | 318 (0.95) | 28.1 (0.79) | 227 (1.82) | 24.6 (0.89) |
| oral BA (%) | 57 | 63 | 86 | 86 | 100 | 67 |
a
Values represent the average n = 2 rats per dose group. Values in parentheses have been corrected for plasma protein binding and represent unbound values.
b
Data from ref (12).