Comparing pharmacokinetic parameters of E2074 between WT and mdr1a/1b KO mice
E2074 dose was 3 mg/kg orally, and the pharmacokinetic parameters represent the mean ± S.E. of three mice.
| WT | mdr1a/1b KO | KO/WT | |
|---|---|---|---|
| tmax (h) | 0.5 | 0.25–1 | 1.2 |
| Cmax (µg/ml) | 0.11 ± 0.01 | 0.10 ± 0.02 | 0.9 |
| AUC (μg·h/ml) | 0.23 ± 0.00 | 0.24 ± 0.04 | 1.0 |
| Kp,brain at 0.5 h | 2.4 | 8.3 | 3.5 |
AUC, area under the plasma concentration curve; E2074, 2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl)oxy]-8-azabicyclo[3.2.1]oct-8-yl}propyl]-4,5-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-one; KO, knockout; Kp,brain, brain to plasma concentration ratio; tmax, time to reach Cmax; WT, wild type.