Table 3.
Pharmacokinetic Parameters of DLX in Plasma and Brain Homogenate After Intranasal and Intravenous Administration of the Optimized in situ Cubo-Gel and Drug Solution
| Pharmacokinetic Parameters | Plasma | Brain Homogenate | ||||||
|---|---|---|---|---|---|---|---|---|
| IN in situ Cubo-Gel | IN Solution | IV Formula (10% PF127) | IV Solution | IN in situ Cubo-Gel | IN Solution | IV Formula (10% PF127) | IV Solution | |
| Cmax (ng/mL)a | 215 ± 7.00 | 239.63 ± 5.70 | 109.03 ± 9.00 | 167.32 ± 4.3 | 51.8 ± 2.2 | 91.14 ± 4.15 | 37.8 ± 0.86 | 102.43 ± 3.67 |
| Tmax (h)b | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
| AUC0-72 (ng.h/mL)a | 457.96 ± 4.53 | 243.14 ± 8.16 | 301.04 ± 9.03 | 443.37 ± 6.5 | 179.62 ± 6.30 | 109.27 ± 5.3 | 106.32 ± 3.7 | 240.47 ± 6.5 |
| AUC0-∞ (ng.h/mL)a | 463.5 ± 5.5 | 245.34 ± 9.7 | 406.13 ± 4.15 | 444.97 ± 8.31 | 233.38 ± 6.5 | 118.99 ± 4.00 | 111.97 ± 3.00 | 287.58 ± 3.7 |
| Relative/Absolute Bioavailability (%) | 188.92c 114.13d 104.16e |
196.13c 208.43d 81.15e |
||||||
| Ke (h−1)a | 0.06 ± 0.01 | 0.05 ± 0.04 | 0.04 ± 0.02 | 0.06 ± 0.04 | 0.01 ± 0.01 | 0.03 ± 0.01 | 0.03 ± 0.03 | 0.01 ± 0.01 |
| t½ (h)a | 12.54 ± 1.26 | 12.80 ± 0.9 | 18.61 ± 0.70 | 10.85 ± 1.85 | 59.2 ± 1.84 | 27.02 ± 1.00 | 25.79 ± 4.90 | 102.43 ± 7.5 |
| MRT (h)a | 9.90 ± 1.00 | 7.92 ± 0.86 | 12.01 ± 1.00 | 5.98 ± 3.00 | 46.43 ± 1.55 | 21.01 ± 2.00 | 11.58 ± 0.70 | 40.93 ± 1.05 |
| BTE% | 137.77 | 75.02 | ||||||
| DTP% | 27.42 | −33.30 | ||||||
Notes: aData are the mean values (n = 3) ± SD. bData are the median value. cCompared to IN Solution. dCompared to IV Formula. eCompared to IV Solution.