TABLE 4.
Murine pharmacokinetic parameters
| Parametera | Value for compound: |
||||
|---|---|---|---|---|---|
| 2 | 11 | 12 | 13 | 14 | |
| i.v.b | |||||
| Dose (mg/kg) | 30 | 15 | 30 | 30 | 30 |
| Cmax (μg/ml) at 5 min | 8.9 | 18.0 | 13.7 | 13.6 | 17.1 |
| CL (ml/h/kg) | 2,180 | 328 | 1,119 | 582 | 687 |
| Vss (ml/kg) | 2,116 | 968 | 3,805 | 3,142 | 3,221 |
| MRT (h) | 2.1 | 3.0 | 3.4 | 5.4 | 4.7 |
| AUC0–∞ (h · μg/ml) | 13.8 | 45.8 | 26.8 | 51.6 | 43.7 |
| α-t1/2 (h) (% AUC) | 0.06 (5) | 0.09 (2) | 0.11 (7) | 0.10 (2) | 0.05 (5) |
| β-t1/2 (h) (% AUC) | 1.5 (95) | 2.08 (98) | 2.53 (93) | 3.83 (98) | 3.40 (95) |
| p.o.c | |||||
| Dose (mg/kg) | 30 | 30 | 30 | 30 | 30 |
| Cmax (μg/ml) | 3.4 | 7.2 | 5.0 | 6.4 | 6.3 |
| Tmax (h) | 0.50 | 1.00 | 1.00 | 0.25 | 0.50 |
| AUC0–24 (h · μg/ml) | 13.2 | 35.9 | 23.8 | 47.5 | 57.6 |
| Terminal t1/2 (h) | 1.8 | 2.7 | 2.7 | 3.1 | 3.6 |
| Bioavailability (%) | 96 | 39 | 89 | 92 | 100 |
| Mouse PPB (%) | 6 | 50 | 16 | 23 | |
a
CL, clearance; Vss, volume of distribution at steady state; MRT, mean residence time; t1/2, half-life; Tmax, time to maximum concentration of drug in serum. PPB, plasma protein binding.
b
WinNonlin two-compartment analysis with iterative weighting.
c
WinNonlin noncompartmental analysis with uniform weighting.