6. Comparison of Pharmacokinetic Parameters for (+)-19m 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 | 0.66 ± 0.47 | 0.318 ± 0.15 | 4.13 ± 1.21 | 2.98 ± 1.74 | n.d. |
| Rat | 1.6 ± 0.24 | 0.577 ± 0.079 | 3.51 ± 0.5 | 3.69 ± 0.19 | 0.579 ± 0.056 |
| Dog | 1.3 ± 0.063 | 1.62 ± 0.147 | 1.24 ± 0.11 | 1.85 ± 0.18 | 0.0002 ± 0.00001 |
| Cyno | 6.8 ± 2.61 | 2.97 ± 0.48 | 0.69 ± 0.12 | 4.36 ± 0.6 | 0.0018 ± 0.006 |
| PO Parameters
(5 mg/kg dose) | |||||
|---|---|---|---|---|---|
| Species | t1/2 (h) | tmax (h) | Cmax (μg/mL) | AUC0‑inf (μg·h/mL) | %F |
| Mouse | 1.5 ± 1.13 | 0.25 ± 0.087 | 0.82 ± 0.19 | 0.91 ± 0.092 | ∼100 |
| Rat | 2.5 ± 1.0 | 0.5 ± 0.43 | 0.45 ± 0.12 | 1.28 ± 0.14 | 89 |
| Dog | 4.0 ± 1.78 | 0.58 ± 0.38 | 1.59 ± 1.02 | 3.92 ± 2.92 | 97 |
| Cyno | 5.52 ± 0.95 | 3.0 ± 0.00 | 0.43 ± 0.059 | 4.30 ± 0.2 | 58 |
a
The mouse (2 mg/kg) and rat (10 mg/kg) PO doses were dose adjusted to 5 mg/kg assuming dose-linearity. %F: % oral bioavailability. AUC0‑inf: area under the curve extrapolated to infinity. Cl: Total clearance. CIR: renal clearance. C max: maximum concentration. Cyno: cynomolgus monkey. iv: intravenous. po: oral administration. t 1/2: half-life. T max: time to maximum concentration. Vss: volume of distribution.