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.
↵a Brain concentrations were estimated by dividing the injectate concentration by the dilution factor of 39.9, as previously reported elsewhere (Kakee et al., 1996).
↵b Percentage of pemetrexed eliminated from the ipsilateral cerebrum at 30 minutes.
↵c Percentage of pemetrexed eliminated from the ipsilateral cerebrum at 60 minutes.
↵d Percentage of control normalized by the value of wild-type mice at 60 minutes.
↵e P < 0.001.