PK parameters (PK population)
| Exposure in patients who received etavopivat . | Tmax, h . | Cmax, ng/mL . | AUC0-24, ng×h/mL . | t½, h∗ . | CL/F, L/h . |
|---|---|---|---|---|---|
| Single dose | |||||
| 700 mg (n = 5) | 2.0 (1.0-4.0) | 2894 (1450); 50.1 | 7552 (3294); 43.6 | 16.9 (7.1); 41.8† | 102.0 (50.8); 49.8† |
| Once-daily multiple doses | |||||
| 300 mg for 2 wk | |||||
| Day 1 (n = 8) | 1.0 (0.9-2.1) | 884 (339); 38.3 | 2508 (995); 39.7‡ | 4.9 (0.9); 18.4‡ | 136.6 (61.5); 45.0‡ |
| Day 14 (n = 7) | -- | 760 (412); 54.2 | 2747 (1047); 38.1 | -- | 123.5 (46.9); 38.0§ |
| 600 mg for 2 wk | |||||
| Day 1 (n = 8) | 1.8 (1.0-4.1) | 1724 (1246); 72.3 | 6177 (2944); 47.7 | 4.0 (0.6); 14.4‖ | 107.2 (45.0); 42.0‖ |
| Day 14 (n = 8) | -- | 3465 (2136); 61.7 | 7728 (4218); 54.6 | -- | 98.8 (50.5); 51.1§ |
| 400 mg for 12 wk | |||||
| Day 1 (n = 15) | 1.8 (1.0-3.9) | 1139 (510); 44.8 | 3474 (1283); 36.9¶ | 4.7 (1.2); 25.6# | 121.8 (31.6); 26.0# |
| Day 84 (n = 13) | -- | 1288 (684); 53.1 | 3105 (901); 29.0∗∗ | -- | 138.2 (37.7); 27.3§,∗∗ |
| Exposure in patients who received etavopivat . | Tmax, h . | Cmax, ng/mL . | AUC0-24, ng×h/mL . | t½, h∗ . | CL/F, L/h . |
|---|---|---|---|---|---|
| Single dose | |||||
| 700 mg (n = 5) | 2.0 (1.0-4.0) | 2894 (1450); 50.1 | 7552 (3294); 43.6 | 16.9 (7.1); 41.8† | 102.0 (50.8); 49.8† |
| Once-daily multiple doses | |||||
| 300 mg for 2 wk | |||||
| Day 1 (n = 8) | 1.0 (0.9-2.1) | 884 (339); 38.3 | 2508 (995); 39.7‡ | 4.9 (0.9); 18.4‡ | 136.6 (61.5); 45.0‡ |
| Day 14 (n = 7) | -- | 760 (412); 54.2 | 2747 (1047); 38.1 | -- | 123.5 (46.9); 38.0§ |
| 600 mg for 2 wk | |||||
| Day 1 (n = 8) | 1.8 (1.0-4.1) | 1724 (1246); 72.3 | 6177 (2944); 47.7 | 4.0 (0.6); 14.4‖ | 107.2 (45.0); 42.0‖ |
| Day 14 (n = 8) | -- | 3465 (2136); 61.7 | 7728 (4218); 54.6 | -- | 98.8 (50.5); 51.1§ |
| 400 mg for 12 wk | |||||
| Day 1 (n = 15) | 1.8 (1.0-3.9) | 1139 (510); 44.8 | 3474 (1283); 36.9¶ | 4.7 (1.2); 25.6# | 121.8 (31.6); 26.0# |
| Day 84 (n = 13) | -- | 1288 (684); 53.1 | 3105 (901); 29.0∗∗ | -- | 138.2 (37.7); 27.3§,∗∗ |
A dash indicates not done. ∗Data are presented as arithmetic mean (± standard deviation) and %CV for Cmax, AUC0-24, t½, and CL/F. Data are presented as median (range) for Tmax.
%CV, percent coefficient of variation; AUC0-24, area under the concentration-time curve from time 0 to 24; CL/F, apparent clearance; Cmax, maximum concentration; PK, pharmacokinetics; t½, terminal elimination half-life; Tmax, time to maximum concentration.
The difference between the 700-mg dose and the 300-mg, 400-mg, and 600-mg doses in estimated t½ is likely due the reduced sampling schedule during the elimination phase of the PK profile in the MAD and OL cohorts.
n = 4.
n = 7.
Steady state.
n = 6.
n = 11.
n = 10.
n = 9.