Table 7.
In Vivo PK and Brain Penetrability for Compound 13a
| In vivo PK profile | ||||
|---|---|---|---|---|
| dose (mg/kg) | T1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUC0–inf (ng·h·mL−1) |
| 10, ip | 2.41 ± 1.73 | 0.5 | 878 ± 236 | 1885 ± 232 |
| 20, po | 2.14 ± 0.18 | 0.667 ± 0.289 | 181 ± 36 | 615 ± 94 |
| Brain penetration analysis | ||||
| dose (mg/kg) | time (h) | brain conc (ng/g) | plasma conc (ng/mL) | brain/plasma ratio |
| 10, ip | 0.25 | 378 ± 58.8 | 642 ± 133 | 0.589 |
| 10, ip | 1.0 | 1120 ± 65 | 547 ± 18.3 | 2.05 |
a
T1/2, half-life; Tmax, time of maximum concentration; Cmax, maximum concentration; AUC0–inf, area under the plasma concentration–time curve; time, hours after dose for brain collection; brain conc, averaged concentration of 13 in tissue sample. Experiments were studied in biological triplicates, and data values are shown as the mean ± SEM (± standard error of the mean) from male Sprague–Dawley rats. Vehicle, 10% dimethyl sulfoxide (DMSO)/90% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD).