Table 8. Pharmacokinetic Profiles of Key Compoundsa.
|
1 |
27 |
35 |
47 |
55 |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| IP | IP | IP | PO | IP | PO | IP | PO | IP | PO | |
| mouse strain | HRN | NMRI | NMRI | NMRI | NMRI | NMRI | NMRI | NMRI | NMRI | NMRI |
| dose (mg/kg) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Cmax (ng/mL) (μM) | 2700 (8.2) | 1100 (3.3) | 590 (1.8) | 87 (0.26) | 910 (2.8) | 180 (0.55) | 2300 (7.4) | 750 (2.4) | 2900 (8.4) | 1500 (4.3) |
| Tmax (h) | 2 | 0.5 | 0.25 | 0.5 | 0.25 | 0.25 | 0.25 | 0.5 | 1.0 | 0.5 |
| AUC0–8 (ng min/mL) (μmol/L·h) | 980,000 (50) | 110,000 (5.6) | 80000 (4.1) | 9000 (0.46) | 110,000 (5.6) | 15,000 (0.8) | 170,000 (9.1) | 61,000 (3.3) | 710,000 (34) | 210,000 (10) |
| t1/2 (h) | 4.8 | 0.7 | 0.9 | 0.9 | 1.1 | 0.7 | 0.5 | 0.6 | 1.2 | 2.0 |
| B:B | ND | 1.3 | 1.5 | 0.9 | 1.4 | |||||
a
B:B = brain to blood ratio (compound dosed intravenously at 0.5 or 1 mg/kg and levels measured after 5 min); ND = not determined; PO = oral; IP = intraperitoneal; AUC = area under the curve; Cmax = the maximum concentration; Tmax is the time at which the maximum concentration is reached; t1/2 is the half-life.