Table 2. Single-Dose Pharmacokinetic Parameters of 6 in Rats, Dogs, and Cynomolgus Monkeysa.
| species | route | dose (mg/kg) | Clp (mL/min/kg) | Vss (L/kg) | t1/2 (hr) | AUC0–24 h (ng/mL*hr) | Cmax (ng/mL) | Tmax (hr) | F (%) |
|---|---|---|---|---|---|---|---|---|---|
| rat | IVb | 1 | 29 ± 4 | 3.0 ± 0.3 | 3 ± 0.4 | 594 ± 98 | |||
| POb,c | 10 | 3969 ± 235 | 813 ± 144 | 1.6 ± 0.4 | 66 | ||||
| dog | IVb | 0.2 | 1.7 ± 0.3 | 2.0 ± 0.2 | 14 ± 2 | 1390 ± 138 | |||
| POb | 1 | 6591 ± 455 | 376 ± 19 | 2 ± 1 | 69 | ||||
| monkey | IVb | 0.2 | 9.3 ± 1.3 | 2.4 ± 0.2 | 4 ± 0.1 | 369 ± 54 | |||
| POb | 1 | 614 ± 110 | 89 ± 4 | 4 ± 1 | 34 |
a
Mean ± SD (n = 3).
b
Formulation IV, and PO, solution in 15%HPCD.
c
Brain/plasma ratio at 4 h = 0.2.