Table 1.
Descriptive pharmacokinetic parameters
| Analyte | Tissue | Tmax (s) | Cmax (ng/ml; ng/g) | t½ (min) | AUC 0→last (min•ng/ml; min•ng/g) | AUC 0→∞ (min•ng/ml; min•ng/g) | AUC brain/AUC plasma 0→last | AUC brain/AUC plasma 0→ ∞ | F |
|---|---|---|---|---|---|---|---|---|---|
| Allopregnanolone | Plasma | 60 | 645 | 16 | 12486 | 13538 | 2.94 | 2.97 | 0.97 |
| Brain | 600 | 845 | 36743 | 40213 | |||||
| Ganaxolone | Plasma | 120* | 550 | 25 | 17285 | 20502 | 2.93 | 3.02 | 0.95 |
| Brain | 600 | 1239 | 50647 | 61952 |
Allopregnanolone and ganaxolone were administered to mice at a dose of 3 mg/kg, i.m. Animals were sacrificed at various time points after injection and blood and brain was collected for analysis. Descriptive pharmacokinetic parameters are Cmax, maximal plasma or brain concentration, where plasma concentration is in ng/ml and brain concentration is in ng/g; Tmax, time to reach Cmax; t½, terminal half-life; AUC 0→last, area under the plasma concentration time curve to the last time point (7200 second) sampled; AUC 0→∞, area under the plasma concentration time curve extrapolated to infinity; F, bioavailability with intramuscular injection determined as the [(plasma AUC 0→∞) × CL1] ÷ 3 mg/kg, where CL1 is from Table 2.
First blood collection was at 120 s; Cmax value corresponds with this initial collection.