TABLE 1.

Effect of various treatments on brain-to-blood transport of pemetrexed

[3H]-Pemetrexed	Concentration in the Injectate (mM)	Concentration in the Brain (mM)a	BEI (%)b	Percentage of Control
WT (control)	—	—	48.9 ± 5.1	100.0
Mrp2−/−	—	—	58.3 ± 3.3c	100.4d
Bcrp1−/−	—	—	43.9 ± 2.1	89.7
WT + pemetrexed	1	0.025	28.3 ± 7.1e	57.8
WT + pemetrexed	50	1.253	4.3 ± 4.8e	8.8
WT + probenecid	100	2.506	27.6 ± 3.3e	56.5
WT + benzylpenicillin	100	2.506	12.2 ± 4.0e	25.0

BEI, brain efflux index; WT, wild type.

^aBrain concentrations were estimated by dividing the injectate concentration by the dilution factor of 39.9, as previously reported elsewhere (Kakee et al., 1996).

^bPercentage of pemetrexed eliminated from the ipsilateral cerebrum at 30 minutes.

^cPercentage of pemetrexed eliminated from the ipsilateral cerebrum at 60 minutes.

^dPercentage of control normalized by the value of wild-type mice at 60 minutes.

^eP < 0.001.