Table 4.
PK Parameters for SRK-181-mIgG1 in C57BL/6 or SRK-181 in Sprague-Dawley Rats and Cynomolgus Monkeys From Non-GLP Single-Dose PK Studies.
| C57BL/6 mice (female) | n = 4/group/time point | 0.3 mg/kg | 3 mg/kg | 10 mg/kg | 30 mg/kg | |
|---|---|---|---|---|---|---|
| Day 1 | Cmax (µg/mL) | 7.40 | 153 | 233 | 664 | |
| Tmax (h) | 8 | 8 | 1 | 1 | ||
| AUC0-t (h*µg/mL) | 0.10 | 4.71 | 17.4 | 64.1 | ||
| t½ (h) | NC | 33.4 | 46.3 | 74.4 | ||
| Sprague-Dawley rats (female) | n = 4/group | 0.3 mg/kg | 1 mg/kg | 3 mg/kg | 10 mg/kg | 30 mg/kg |
| Day 1 | Cmax (µg/mL) | 6.31 | 20.3 | 78.4 | 263 | 873 |
| Tmax (h) | 1 | 1 | 1 | 1 | 1 | |
| AUC0-t (h*µg/mL) | 221 | 1,230 | 5,830 | 26,000 | 135,000 | |
| t½ (h) | 24 | 43.7 | 48.7 | 37.0 | 31.4 | |
| Cynomolgus monkeys (female) | n = 3/group | 1 mg/kg | 3 mg/kg | 10 mg/kg | 30 mg/kg | |
| Day 1 | Cmax (µg/mL) | 25.2 | 82.2 | 287 | 909 | |
| Tmax (h) | 1 | 1 | 1 | 1 | ||
| AUC0-t (h*µg/mL) | 1,760 | 7,850 | 28,800 | 135,000 | ||
| t½ (h) | 53.8 | 73.9 | 119 | 111 | ||
| CL (mL/h/kg) | 0.535 | 0.363 | 0.307 | 0.223 | ||
| VSS (mL/kg) | 47.1 | 44.5 | 53.7 | 56.3 |
Abbreviations: AUC0-t, area under the curve from time 0 to tlast; CL, clearance; Cmax, maximum observed concentration; NC, not calculated; PK, pharmacokinetics; t½, elimination half-life; Tmax, time of maximum observed concentration; Vss, volume of distribution at steady state.