Table 5.

Calculated individual pharmacokinetic properties of IBR and the active moiety (IBR + DIB). AUC_0–24, area under the concentration–time curve from dose intake to 24 h postdose. AUMC_0–24, area under the first moment of the concentration–time curve from dose intake to 24 h postdose. CL/F, apparent clearance. c_max, peak concentration. K_e, terminal elimination rate constant. MRT_0–24, mean residence time from dose intake to 24 h postdose. t_1/2, systemic half-life. t_max, time to reach the peak concentration. V/F, apparent volume of distribution.

Parameter	Ibrutinib			Dihydrodiol Ibrutinib			Ibrutinib + Dihydrodiol Ibrutinib
	Patient 1	Patient 2	Patient 3	Patient 1	Patient 2	Patient 3	Patient 1	Patient 2	Patient 3
AUC0–24 (nmol × L/h)	1786	1740	613	2347	2528	1800	4134	4268	2414
AUMC0–24 (nmol × L)	7488	7434	2051	16,593	11,626	8172	24,082	19,071	10,230
cmax (nmol/L)	265.6	374.0	163.2	184.7	253.7	216.6	450.3	627.7	358.3
Dose-normalized cmax [nmol/(L × mmol)]	278.7	392.4	256.6	Cannot be calculated			472.5	658.6	563.3
tmax (h)	2.0	1.0	1.0	2.0	1.0	2.0	2.0	1.0	1.0
CL/F (L/h)	515	523	1008	Cannot be calculated			Cannot be calculated
MRT0–24 (h)	4.19	4.28	3.34	7.07	4.60	4.54	5.82	4.47	4.24
ke (1/h)	0.126	0.113	0.121	0.069	0.130	0.122	0.085	0.123	0.122
t1/2 (h)	5.49	6.12	5.74	10.1	5.35	5.68	8.13	5.64	5.70
V/F (L)	4080	4620	8346	Cannot be calculated			Cannot be calculated