TABLE 3

Steady-state plasma and brain concentration, brain-to-plasma ratio, and distribution advantage of ponatinib after continuous intraperitoneal infusion (40 µg/h) for 48 h in FVB wild-type, Bcrp1(−/−), Mdr1a/b(−/−), and Mdr1a/b(−/−)Bcrp1(−/−) mice (N = 4 in each genotype)

Data are presented as the mean ± S.D, unless otherwise indicated.

Mice	Steady-State Total Concentration (μg/ml)		Kp	Kp,uu^{^a}	DA^{^b}
Mice	Plasma	Brain	Kp	Kp,uu^{^a}	DA^{^b}
FVB wild-type	0.72 ± 0.66	0.53 ± 0.37	1.0 ± 0.51	0.11 ± 0.056
Bcrp1(−/−)	0.42 ± 0.21	0.71 ± 0.30	1.8 ± 0.26	0.20 ± 0.029	1.7
Mdr1a/b(−/−)	0.39 ± 0.14	1.3 ± 0.70	3.8 ± 2.5	0.42 ± 0.28	3.7
Mdr1a/b(−/−)Bcrp1(−/−)	0.40 ± 0.34	6.1 ± 5.0^*	15.6 ± 2.6^*	1.7 ± 0.29^*	15.0

↵^a Calculated by Kp × [f_u,brain/f_u,plasma].
↵^b DA due to lack of transporters, or Kp,knockout/Kp,wild-type or Kp,uu,knockout/Kp,uu,wild-type.
↵* Statistical difference (P < 0.05) compared with the FVB wild-type mice.