TABLE 4

Pharmacokinetic metrics in FVB wild-type and Mdr1a/b−/−Bcrp1−/− mice after oral dosing with 25 mg/kg dabrafenib

Data are presented as the mean ± S.D.

Mouse GenotypeTissueCmaxAUClastaKpKp Ratiob
µg/mlµg × min/ml
Wild-typePlasma0.143 ± 0.01415.8 ± 3.00.0445.7
Wild-typeBrain0.007 ± 0.0010.69 ± 0.22
Mdr1a/b−/−Bcrp1−/−Plasma0.324 ± 0.08531.1 ± 5.1c0.25
Mdr1a/b−/−Bcrp1−/−Brain0.098 ± 0.0227.6 ± 1.3d
  • AUC, area under the curve; FVB, Friend leukemia virus strain B; Kp, AUCbrain/AUCplasma.

  • a Area under the curve from time zero to 4 hours postdose.

  • b Kp in Mdr1a/b−/−Bcrp1−/− mice/Kp in wild-type mice.

  • c P = 0.0414 compared with wild-type plasma.

  • d P = 0.002 compared with wild-type brain.