TABLE 3.

Comparison of pharmacokinetic parameters of dabrafenib in FVB wild-type and Mdr1a/b^−/−Bcrp1^−/− mice after an i.v. dose of 2.5 mg/kg

	Wild Type		Mdr1a/b−/−Bcrp1−/− Mice
	Plasma	Brain	Plasma	Brain
Terminal rate constant (min−1)	0.03	0.036	0.024	0.026
Half-life (min)	23.7	19.1	28.3	26.6
Clearance (ml/min/kg)	24.2		28.4
Volume of distribution (l/kg)	0.83		1.2
AUC0 → t last (µg · min /ml)a	120.9 ± 15.8	2.8 ± 0.4	101.4 ± 8.7	42.1 ± 3.4b
Kp	0.023		0.42
Kp ratioc	18.3

AUC, area under the concentration-time curve; FVB, Friend leukemia virus strain B; K_p, AUC_brain/AUC_plasma.

^aArea under the curve from time zero to 2 hours postdose.

^bP < 0.05 compared with wild-type AUC_brain.

^cK_p ratio = (K_p in Mdr1a/b^−/−Bcrp1^−/− mice) / (K_p in wild-type mice).