Parameter | Strain | ||
---|---|---|---|
Wild Type | Abcb1a/1b(+/−);Abcg2(+/−) | Abcb1a/1b(−/−);Abcg2(−/−) | |
AUC0–6 h, ng/ml.h | 238.9 ± 88.7 | 357.4 ± 80.4 | 183.7 ± 41.2a |
Fold change AUC0–6 h | 1.0 | 1.5 | 0.8 |
Cmax, ng/ml | 55.5 ± 33.4 | 77.2 ± 16.0 | 37.6 ± 11.2 |
Tmax, h | 2.00 | 4.00 | 1.00 |
Cbrain, ng/g | 36.5 ± 17.5 | 88.4 ± 11.7b | 721.3 ± 337.8c,d |
Fold increase Cbrain | 1.0 | 2.4 | 19.7 |
Pbrain (*10−2 h−1) | 16.4 ± 10.1 | 25.8 ± 6.6 | 389.1 ± 153.4c,d |
Fold increase Pbrain | 1.0 | 1.6 | 23.7 |
AUC0–6 h, area under the plasma concentration-time curve from 0 to 6 hours; Cmax, maximum plasma concentration; Tmax, time to reach maximum drug concentration in plasma; Cbrain, brain concentration of drug at 6 hours after oral administration; Pbrain, relative brain accumulation of drug at 6 hours after oral administration, calculated by determining the drug brain concentration relative to the AUC0–6 h.
↵a P < 0.01 compared with Abcb1a/1b(+/−);Abcg2(+/−) mice.
↵b P < 0.05 compared with wild-type mice.
↵c P < 0.001 compared with wild-type mice.
↵d P < 0.001 compared with Abcb1a/1b(+/−);Abcg2(+/−) mice.