Pharmacokinetic parameters, brain concentrations, and relative brain accumulation of sorafenib after oral administration at 10 mg/kg
Genotype | ||||
---|---|---|---|---|
WT | Abcb1a/1b−/− | Abcg2−/− | Abcb1a/1b/Abcg2−/− | |
AUC(0–6), μg/mL h | 24.0 ± 4.8 | 19.6 ± 0.7 | 22.2 ± 1.5 | 21.2 ± 2.3 |
Cmax, μg/mL | 6.9 ± 1.3 | 6.7 ± 0.8 | 7.1 ± 0.6 | 6.0 ± 0.8 |
Tmax, h | 1 | 1 | 1 | 2 |
Cbrain, μg/g | 0.12 ± 0.04 | 0.11 ± 0.04 | 0.50 ± 0.13* | 1.04 ± 0.08*,† |
Fold increase | 1.0 | 0.9 | 4.2 | 8.7 |
Pbrain (×10−3 h−1) | 5.3 ± 2.7 | 5.8 ± 2.2 | 22.6 ± 5.0* | 49.4 ± 5.2*,† |
Fold increase | 1.0 | 1.1 | 4.3 | 9.3 |
NOTE: AUC(0–6), area under plasma concentration-time curve up to 6 h; Cmax, maximum plasma concentration; Tmax, time of maximal plasma concentration; Cbrain, brain concentration at 6 h after oral administration; Pbrain, relative brain accumulation at 6 h after oral administration, calculated by determining the sorafenib brain concentration relative to the AUC0–6. Data are means ± SD (n = 5).