TABLE 5.
Pharmacokinetic measurements of DB745 after single i.v. or p.o. administration in mice
| Parametera | Pharmacokinetic measurement of DB745 after indicated dose (μmol/kg) administration |
||||
|---|---|---|---|---|---|
| i.v. |
p.o. |
||||
| 1.5 (1.0 mg salt/kg) | 7.5 (4.9 mg salt/kg) | 25 (16.5 mg salt/kg) | 100 (66 mg salt/kg) | 200 (131 mg salt/kg) | |
| AUC0-∞ (h · μM) | 0.56 | 4.5 | 0.5 | 5.6 | 30.0 |
| AUC_%Extrap (%) | 9 | 3 | 42 | 19 | 13 |
| Cmax (μM) | 0.37 | 4.24 | 0.02 | 0.40 | 1.68 |
| Tmax (h) | 0.0833 | 0.0833 | 2 | 2 | 2 |
| t1/2 (h) | 17 | 18 | 24 | 30 | 32 |
| CL (ml/min/kg)b | 45 | 28 | 28 | 28 | 28 |
| Vss (liter/kg)c | 36 | 22 | 57 | 71 | 76 |
| F (%)d | 3.3 | 9.3 | 25 | ||
a
Noncompartmental analysis by WinNonlin 5.0.1, 1/y weighting, linear up/log down.
b
Observed total body clearance; for p.o. administration, corrected with F.
c
Predicted steady-state volume of distribution for i.v. administration; predicted volume of distribution based on terminal phase.
d
Calculated based on the AUC at 7.5 μmol/kg i.v.