TABLE 4.
Arithmetic mean for PK parameters for SPR206 after multiple ascending doses on day 1 and day 7 or day 14 (PK population)
| Day and parameter | SPR206 (mean ± SD) | ||||
|---|---|---|---|---|---|
| Day 1 | 25 mg q8h × 7 days (n = 6) | 50 mg q8h × 7 days (n = 6) | 100 mg q8h × 7 days (n = 6) | 150 mg q8h × 7 days (n = 6) | 100 mg q8h × 14 days (n = 6) |
| Cmax (ng/ml) | 1,410 ± 241 | 2,525 ± 413 | 5,433 ± 678 | 8,990 ± 1,056 | 5,065 ± 1,003 |
| Tmax (h)a | 1.1 (1.0, 1.3) | 1.1 (1.1, 1.3) | 1.1 (1.0, 1.1) | 1.1 (1.0, 1.1) | 1.1 (1.0, 1.3) |
| AUC0–8 (h · ng/ml) | 4,391 ± 740 | 7,955 ± 951 | 16,544 ± 2,337 | 27,492 ± 3,452 | 15,573 ± 1,765 |
| AUC0–inf (h · ng/ml) | 5,197 ± 945 | 9,243 ± 1,417 | 19,171 ± 2,874 | 30,981 ± 4,189 | 18,184 ± 1,244 |
| Half-life (h) | 2.7 ± 0.2 | 2.7 ± 0.3 | 2.7 ± 0.2 | 2.4 ± 0.2 | 2.5 ± 0.2 |
| CL (liters/h) | 4.9 ± 0.9 | 5.5 ± 0.8 | 5.3 ± 0.8 | 4.9 ± 0.6 | 5.5 ± 0.4 |
| Vz (liters) | 18.9 ± 2.6 | 21.5 ± 1.8 | 20.8 ± 2.9 | 17.1 ± 2.1 | 19.9 ± 3.0 |
| Day 7 or day 14 | 25 mg q8h × 7 days (n = 6) | 50 mg q8h × 7 days (n = 6) | 100 mg q8h × 7 days (n = 6) | 150 mg q8h × 7 days (n = 6) | 100 mg q8h × 14 days (n = 6) |
| Cmax (ng/ml) | 1,607 ± 300 | 2,897 ± 270 | 6,345 ± 1099 | 11,518 ± 1,901 | 6,423 ± 841 |
| Tmax (h)a | 1.1 (1.0, 1.3) | 1.1 (1.0, 1.2) | 1.1 (1.0, 1.1) | 1.1 (1.1, 1.1) | 1.1 (1.0, 1.1) |
| AUC0–8 (h · ng/ml) | 5,881 ± 1,166 | 10,050 ± 1,050 | 21,340 ± 2,857 | 41,475 ± 6,083 | 22,277 ± 2,574 |
| AUC0–48 (h · ng/ml) | 7,681 ± 1,726 | 12,435 ± 1,796 | 27,531 ± 4,610 | 55,505 ± 7,838 | 29,828 ± 5,112 |
| AUC0–inf (h · ng/ml) | 7,690 ± 1,732 | 12,443 ± 1,802 | 27,671 ± 4,762 | 56,007 ± 7,874 | 30,412 ± 5,699 |
| AUC%ext (h · ng/ml) | 10.0 ± 4.5 | 6.9 ± 2.5 | 1.9 ± 0.4 | 0.9 ± 0.1 | 3.3 ± 1.4 |
| Half-life (h) | 4.0 ± 0.6 | 3.5 ± 0.9 | 5.3 ± 1.4 | 5.9 ± 0.3 | 9.6 ± 8.1 |
| CL (liters/h) | 4.4 ± 0.9 | 5.0 ± 0.5 | 4.8 ± 0.6 | 3.7 ± 0.5 | 4.5 ± 0.5 |
| Vz (liters) | 21.3 ± 3.6 | 21.5 ± 2.2 | 22.5 ± 3.5 | 19.6 ± 3.2 | 23.9 ± 4.0 |
a
Median (range).