Table 4. PK Parameters and NaV1.7 Coverage in Mice.
| PK parameters
in ddY mice at 1 mg/kga |
||||||||
|---|---|---|---|---|---|---|---|---|
| Cmax (μM) | Tmax (h) | AUC0–24h (h·μM) | T1/2 (h) | CL (mL/min/kg) | Vss (L/kg) | F (%) | Mouse NaV1.7 coverage (Fold)b | |
| 1p | 1.7 ± 0.39c | 1.0 ± 0.87c | 12.1 ± 2.1c | 5.0 ± 2.6c | 2.58 ± 0.33c | 0.57 ± 0.03c | 65 ± 12c | <0.0042 |
| 2e | 2.3 ± 0.14c | 3.3 ± 4.0c | 41.5 ± 2.4c | 17.0 ± 6.1c | 1.01 ± 0.15c | 0.81 ± 0.05c | 117 ± 23c | 0.20 |
| 2g | 1.4 (1.5, 1.4)d | 6.0 (6.0, 6.0)d | 23.6 (24.0, 23.3)d | 13.5 (11.6, 15.5)d | NTe | NTe | NTe | 0.65 |
a
The test compounds in 0.5% MC were administered to ddY mice at 1 mg/kg (p.o.). Total body clearance (CL), distribution volume at a steady state (Vss), and F value were calculated after intravenous (1 mg/kg) administration of the test compounds. Each value represents the mean ± SD.
b
Mouse NaV1.7 coverage = plasma Cmax_free/mNaV1.7 IC50.
c
n = 3.
d
Individual data (n = 2).
e
Not tested.