TABLE 1.
Summary of pharmacokinetic parameters in plasma, brain, and spinal cord in FVB wild-type, BKO, PKO, and TKO mice after an intravenous bolus dose of 5 mg/kg AZD1390
| Parameter | Units | Plasma | Brain | Spinal Cord | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Wild-Type | Bcrp1−/− | Mdr1a/b−/− | Mdr1a/b−/− Bcrp1−/− | Wild-Type | Bcrp1 −/− | Mdr1a/b−/− | Mdr1a/b−/− Bcrp1−/− | Wild-Type | Bcrp1−/− | Mdr1a/b−/− | Mdr1a/b−/− Bcrp1−/− | ||
| t 1/2 | hour | 2.6 | 2.4 | 2.8 | 2.5 | 2.0 | 1.8 | 3.0 | 2.4 | 2.1 | 2.1 | 2.7 | 2.5 |
| CL | l/hr/kg | 0.95 | 0.88 | 0.97 | 0.92 | ||||||||
| Vss | l/kg | 2.7 | 2.7 | 3.0 | 2.9 | ||||||||
| AUC0–∞ | hr*ng/ml | 5261 ± 295 | 5690 ± 197 | 5178 ± 361 | 5452 ± 306 | 1542 ± 111 | 1814 ± 97 | 16,221 ± 752 | 17,043 ± 684 | 1684 ± 129 | 1960 ± 128 | 13,949 ± 718 | 16,566 ± 445 |
| Kp | 0.29 | 0.32 | 3.13 | 3.13 | 0.32 | 0.34 | 2.7 | 3.03 | |||||
| fu | 0.203 ± 0.025 | 0.075 ± 0.002 | 0.11 ± 0.008 | ||||||||||
| Kpuu | 0.1 | 0.12 | 1.16 | 1.16 | 0.17 | 0.18 | 1.46 | 1.64 | |||||
| DAfree | 1 | 1.2 | 11.6 | 11.6 | 1 | 1.1 | 8.6 | 9.6 | |||||