Table 3.
Schedule A 110 mg/m2 |
Schedule B 196 mg/m2 |
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---|---|---|---|---|
Parameter | Day 1, n=13 | Day 9, n=9 | Day 1, n=7 | Day 4, n=6 |
Cmax, ng/mL | 1502 (33) | 1683 (28) | 4565 (24) | 3751 (53) |
Tmax, hr | 1.02 (1.0–1.3) | 1.08 (1.0– 1.1) | 1.1 (1.0–1.1) | 1.02 (0.9– 1.1) |
AUC0-24hr, nghr/mL | 4685 (23) | 4833 (19)a | 10,830 (19)b | 8309 (39) |
AUC0-τ, nghr/mL | 4685 (23) | 4833 (19)a | 12,367 (13)c | NE |
t½, hr | NE | NE | 8.5 (0.6)d | NE |
CLp, L/hr | NE | NE | 28.3 (3)e | NE |
Vss, L | NE | NE | 158 (9)e | NE |
Parameters are reported as geometric mean (% coefficient of variation), except for Tmax, which is reported as median (range), and t½, which is reported as the arithmetic mean (standard deviation).
n=7,
n=6,
n=4,
n=5,
n=3.
NE, not estimated. Due to limited time points in the terminal disposition phase, an estimate of pevonedistat elimination half-life could not be obtained for schedule A.
Cmax, maximum observed concentration; Tmax, time to reach Cmax; AUC0–24hr/AUC0-τ, area under the concentration–time curve from time zero to 24 hours / to the end of dosing interval, where the dosing interval, τ, is equal to 24 and 72 hours for schedules A and B, respectively; t½, terminal disposition half-life; CLp, plasma clearance; Vss, steady-state volume of distribution.