Table 3.
Pharmacokinetic parameters in multiple-dose cohorts
| Parameter | 50 mg, n = 5 | 100 mg, n = 5 | 200 mg, n = 5 | 100 mg (bid), n = 5 |
|---|---|---|---|---|
| Day 1 | ||||
| AUC0-t (ng · h/ml) | 276 ± 102 | 458 ± 152 | 1554 ± 284 | 675 ± 131 |
| AUC0-∞ (ng · h/ml) | 283 ± 104 | 466 ± 150 | 1560 ± 285 | 685 ± 128 |
| Cmax (ng/ml) | 103 ± 52 | 205 ± 90 | 721 ± 121 | 281 ± 93 |
| Tmax (h) | 0.5 (0.5 – 2.0) | 0.5 (0.4 – 1.0) | 0.5 (0.3 – 0.5) | 0.7 (0.5 – 1.0) |
| t1/2 (h) | 5.7 ± 3.1 | 4.8 ± 2.6 | 4.2 ± 0.6 | 2.4 ± 0.6 |
| MRT (h) | 3.9 ± 1.1 | 3.2 ± 0.3 | 2.7 ± 0.3 | 2.5 ± 0.5 |
| Day 7 | ||||
| AUC0-t (ng · h/ml) | 305 ± 154 | 497 ± 115 | 1513 ± 199 | 690 ± 168 |
| AUC0-∞ (ng · h/ml) | 314 ± 162 | 507 ± 113 | 1530 ± 201 | 704 ± 169 |
| Cmax (ng/ml) | 112 ± 59 | 228 ± 96 | 626 ± 195 | 250 ± 72 |
| Tmax (h) | 0.6 (0.5 – 1.0) | 0.5 (0.5 – 0.5) | 0.5 (0.5 – 1.1) | 0.5 (0.5 – 1.0) |
| t1/2 (h) | 8.2 ± 6.9 | 7.0 ± 4.3 | 10.8 ± 14.0 | 2.2 ± 0.5 |
| MRT (h) | 4.1 ± 0.9 | 3.1 ± 0.8 | 3.3 ± 1.0 | 2.9 ± 0.3 |
Data are presented as mean ± sd, except for Tmax, which is presented as median (range). Pharmacokinetics parameter values for the 100-mg bid dose group were determined from data in the first 12 h after administration of compound and reflect the morning dose (100 mg) only. Most of the AUC from the afternoon dose would not have been measured due to the lack of blood samples between 12 and 24 h. MRT, Mean residence time.