Pharmacokinetic parameters, brain concentrations (t = 6 h), and relative brain accumulation of N-desethyl sunitinib after oral administration of 10 mg/kg sunitinib malate to various mouse strains
| Genotype | ||||
|---|---|---|---|---|
| Wild Type | Abcb1a/1b(−/−) | Abcg2(−/−) | Abcb1a/1b(−/−)/Abcg2(−/−) | |
| Plasma AUC(0–6), ng · h/ml | 152 ± 12.9 | 170 ± 49.6 | 125 ± 66.4 | 95.8 ± 41.1 |
| Fold change AUC(0–6) | 1.00 | 1.12 | 0.82 | 0.63 |
| Sunitinib AUC(0–6), ng · h/mla | 445 ± 203 | 514 ± 145 | 311 ± 172 | 288 ± 88 |
| N-desethyl sunitinib-to-sunitinib AUC ratio | 0.34 | 0.33 | 0.40 | 0.33 |
| Cmax, ng/ml | 36.3 ± 4.00 | 33.6 ± 7.00 | 24.9 ± 12.4 | 24.8 ± 15.2 |
| Cbrain, ng/g | 10.1 ± 0.94 | 11.8 ± 5.20 | 13.2 ± 2.20 | 80.7 ± 40.0** |
| Fold change Cbrain | 1.00 | 1.20 | 1.30 | 8.00 |
| Pbrain, ×10−1 h−1 | 0.67 ± 0.12 | 0.73 ± 0.34 | 1.27 ± 0.60 | 9.20 ± 5.90* |
| Fold change Pbrain | 1.00 | 1.10 | 1.90 | 13.7 |
Cbrain, brain concentration; Pbrain, relative brain accumulation at 6 h after oral administration, calculated by determining the N-desethyl sunitinib brain concentration relative to the AUC(0–6).
↵a Sunitinib AUC data for comparison were taken from Tang et al. (2012).
↵* , P < 0.05;
↵** , P < 0.01, compared with wild-type mice (one-way ANOVA). Data are means (n = 3–7) ± S.D.