Table 1.

Pharmacokinetic parameters, brain concentrations, and relative brain accumulation of sorafenib after oral administration at 10 mg/kg

Genotype
WTAbcb1a/1b−/−Abcg2−/−Abcb1a/1b/Abcg2−/−
AUC(0–6), μg/mL h24.0 ± 4.819.6 ± 0.722.2 ± 1.521.2 ± 2.3
Cmax, μg/mL6.9 ± 1.36.7 ± 0.87.1 ± 0.66.0 ± 0.8
Tmax, h1112
Cbrain, μg/g0.12 ± 0.040.11 ± 0.040.50 ± 0.13*1.04 ± 0.08*,
Fold increase1.00.94.28.7
Pbrain (×10−3 h−1)5.3 ± 2.75.8 ± 2.222.6 ± 5.0*49.4 ± 5.2*,
Fold increase1.01.14.39.3

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).

  • *P < 0.001, compared with WT mice.

  • P < 0.01, compared with Abcg2−/− mice.