TABLE 1

Summary of the plasma and brain concentrations and plasma clearance of lapatinib in Mdr1a/1b(–/–), Bcrp1(–/–), and Mdr1a/b(–/–)/Bcrp1(–/–) knockout mice and FVBn (wild-type) mice after a constant-rate intravenous infusion of lapatinib at 0.3 and 3 mg/kg/h

Data are presented as the mean ± S.D. Statistical difference was declared when p ≤ 0.05.

		Lapatinib Infusion Rate: 0.3 mg/kg/h
Genotype	Mice per Group	Plasma C_ss	Brain Concentration	Brain-to-Plasma Ratio	Plasma Clearance
		ng/ml	ng/ml		ml/min/kg
FVBn	5	730 ± 410	18 ± 9.1	0.03 ± 0.01	13 ± 6.1
Mdr1a/b(-/-)	4	239 ± 43^a^,^b	21 ± 3.3^c	0.09 ± 0.02^a^,^b^,^c	31 ± 4.2^a^,^b
Bcrp1(-/-)	5	394 ± 74^a	17 ± 3.1^d	0.04 ± 0.01^a^,^d	20 ± 4.6^a
Mdr1a/b(-/-) /Bcrp1(-/-)	5	296 ± 150^a	319 ± 67^a	1.2 ± 0.42^a	28 ± 13^a
FVBn	4	5097 ± 2729	194 ± 65	0.04 ± 0.02	20 ± 13
Mdr1a/b(-/-)	3	4463 ± 811^c	732 ± 421^a^,^b^,^c	0.16 ± 0.06^a^,^b^,^c	15 ± 2.3^c
Bcrp1(-/-)	5	6447 ± 2731^d	253 ± 23^a^,^d	0.04 ± 0.01^d	13 ± 4.4^d
Mdr1a/b(-/-) /Bcrp1(-/-)	5	2840 ± 867	4938 ± 1823^a	1.7 ± 0.50^a	23 ± 6.2

↵ a FVBn compared with Mdr1a/b(-/-), Bcrp1(-/-), or Mdr1a/b(-/-)/Bcrp1(-/-).
↵ b Mdr1a/b(-/-) compared with Bcrp1(-/-).
↵ c Mdr1a/b(-/-)/Bcrp1(-/-) compared with Mdr1a/b(-/-).
↵ d Mdr1a/b(-/-)/Bcrp1(-/-) compared with Bcrp1(-/-).