. Author manuscript; available in PMC: 2017 Nov 18.

Published in final edited form as: Clin Cancer Res. 2015 Nov 11;22(1):34–43. doi: 10.1158/1078-0432.CCR-15-1237

Table 3.

Pharmacokinetic parameters of pevonedistat during cycle 1 in patients receiving pevonedistat at the MTD determined in each schedule

	Schedule A 110 mg/m²		Schedule B 196 mg/m²
Parameter	Day 1, n=13	Day 9, n=9	Day 1, n=7	Day 4, n=6
C_max, ng/mL	1502 (33)	1683 (28)	4565 (24)	3751 (53)
T_max, 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)
AUC_0-24hr, nghr/mL	4685 (23)	4833 (19)^a	10,830 (19)^b	8309 (39)
AUC_0-τ, nghr/mL	4685 (23)	4833 (19)^a	12,367 (13)^c	NE
t_½, hr	NE	NE	8.5 (0.6)^d	NE
CL_p, L/hr	NE	NE	28.3 (3)^e	NE
V_ss, L	NE	NE	158 (9)^e	NE

Parameters are reported as geometric mean (% coefficient of variation), except for T_max, which is reported as median (range), and t_½, 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.

C_max, maximum observed concentration; T_max, time to reach C_max; AUC_0–24hr/AUC_0-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; t_½, terminal disposition half-life; CL_p, plasma clearance; V_ss, steady-state volume of distribution.