3. IV and PO PK Parameters for 7b in Multiple Species .
| IV Parameters
(2 mg/kg dose) | |||||
|---|---|---|---|---|---|
| Species | t1/2 (h) | AUC0‑inf (μg·h/mL) | Cl (L/h/kg) | Vss (L/kg) | ClR (L/h/kg) |
| Mouse | 0.41 | 0.34 | 5.94 | 2.44 | n.d. |
| Rat | 0.56 ± 0.05 | 0.77 ± 0.13 | 2.66 ± 0.47 | 1.89 ± 0.34 | 1.44 ± 0.50 |
| Dog | 1.38 ± 0.48 | 1.83 ± 0.08 | 1.10 ± 0.05 | 1.41 ± 0.18 | 0.07 ± 0.08 |
| Cyno | 1.49 ± 0.18 | 2.0 ± 0.18 | 1.0 ± 0.1 | 1.80 ± 0.35 | 0.27 ± 0.19 |
| PO Parameters
(5 mg/kg dose) | |||||
|---|---|---|---|---|---|
| Species | t1/2 (h) | tmax (h) | Cmax (μg/mL) | AUC0‑inf (μg·h/mL) | %F |
| Mouse | 0.6 | 0.25 | 0.94 | 0.72 | 85.6 |
| Rat | 1.51 ± 0.66 | 0.58 ± 0.38 | 0.57 ± 0.08 | 2.02 ± 0.13 | 105 ± 7 |
| Dog | 1.90 ± 0.43 | 0.92 ± 0.95 | 1.82 ± 0.60 | 4.13 ± 1.27 | 90.2 ± 27.8 |
| Cyno | 2.07 ± 0.97 | 2.33 ± 1.53 | 0.70 ± 0.33 | 3.58 ± 1.18 | 71.2 ± 23.4 |
a
%F: % oral bioavailability. AUC0‑inf: area under the curve extrapolated to infinity. C max: maximum concentration. Cyno: cynomolgus monkey. IV: intravenous. n.d.: not determined. PO: oral administration. t 1/2: half-life. T max: time to maximum concentration.