TABLE 1.
Plasma and brain pharmacokinetic parameters determined by noncompartmental analysis after the administration of a single oral dose of sunitinib (20 mg/kg) in wild-type, Mdr1a/b(−/−), Bcrp1(−/−), and Mdr1a/b(−/−)Bcrp1(−/−) mice
Results are expressed as the mean ± S.D. (n = 3–4).
| Parameter | FVB Wild Type | Mdr1a/b(−/−) | Bcrp1(−/−) | Mdr1a/b(−/−)Bcrp1(−/−) |
|---|---|---|---|---|
| Plasma | ||||
| Cmax (μg/ml) | 0.32 ± 0.08 | 0.42 ± 0.13 | 0.225 ± 0.09 | 0.38 ± 0.04 |
| Half-life (h)a | 1.8 | 2.1 | 3.0 | 2.8 |
| Tmax (h) | 1 | 0.5 | 2 | 2 |
| CL/F (ml/min) | 4.6 | 4.1 | 5.1 | 6.5 |
| AUC0-tlast (h-μg/ml) | 1.85 ± 0.36 | 2.26 ± 0.26 | 1.81 ± 0.20 | 1.39 ± 0.12 |
| AUC0-∞ (h-μg/ml) | 1.85 | 2.27 | 1.83 | 1.40 |
| Brain | ||||
| Cmax (μg/ml) | 0.13 ± 0.04 | 0.52 ± 0.14 | 0.20 ± 0.02 | 4.92 ± 0.74 |
| Half-life (h)a | 2.0 | 2.5 | 3.2 | 3.0 |
| Tmax (h) | 4 | 4 | 6 | 2 |
| AUC(0-tlast) (h-μg/ml) | 0.76 ± 0.11 | 3.63 ± 0.15 | 1.58 ± 0.15 | 28.43 ± 3.10 |
| AUC(0-∞) (h-μg/ml) | 0.77 | 3.65 | 1.61 | 28.8 |
| Brain/plasma ratio | ||||
| AUCBrain/AUCPlasma | 0.42 | 1.61 | 0.88 | 20.53 |
| DTI | 3.9 | 2.1 | 48.9 |
CL/F, apparent clearance.
a
Time taken to reach one-half of its steady-state value.