TABLE 5.

Pharmacokinetic parameters for ESM‐HDAC391 and HDAC189 (Part B)

Part B	ESM‐HDAC391 (n = 6 unless otherwise stated)
	Cohort 1 (20 mg)		Cohort 2 (40 mg)
	Day 1	Day 7 e	Day 1	Day 7 h
Cmax	102.54	108.81	165.5	283.84
(ng/mL)	(51.3)	(40.8)	(70.7)	(30.3)
Tmax g	0.500	0.625	0.625	0.625
(h)	(0.25–1.25)	(0.50–2.00)	(0.50–2.00)	(0.50–1.00)
AUC0‐t	76.695	94.351	137.736	228.723
(ng.h/mL)	(39.5)	(31.4)	(41.7)	(27.3)
AUCtau	85.654 b	98.844 a	159.639 a	251.381 b
(ng.h/mL)	(43.8)	(36.9)	(36.1)	(17.4)
t½	NC	0.368 a	NC	0.408 b
(h)		(24.1)		(17.6)
CL/F	NC	0.723 a	NC	159.118 b
(L/h)		(30.3)		(17.4)
Vz/F	NC	107.083 a	NC	93.470 b
(L)		(43.6)		(20.7)
Rac g	NC	1.140 c	NC	1.410 c
		(0.99–1.57)		(1.22–2.45)
Rcmax g	NC	0.9	NC	1.775
		(0.53–2.48)		(0.61–4.78)

Part B	HDAC189 (n = 8 unless otherwise stated)
	Cohort 1 (20 mg)		Cohort 2 (40 mg)
	Day 1	Day 7	Day 1	Day 7
Cmax	78.01	69.47	151.46	180.98
(ng/mL)	(35.6)	(39.6)	(33.1)	(31.9)
Tmax g	1.000	1.125	1.015	1.125
(h)	(0.75–2.00)	(1.00–2.00)	(0.75–2.00)	(0.75–2.00)
AUC0‐t	97.850	89.376	221.401	316.144
(ng.h/mL)	(36.6)	(24.3)	(36.3)	(21.4)
AUC0‐tau	136.873 g	NC	307.974 d	380.624 e
(ng.h/mL)	(1.4)		(0.3)	(14.5)
t½	NC	NC	NC	0.754 e
(h)				(11.7)
Rac g	NC	NC	NC	1.020 f
Rcmax g	NC	0.835 (0.60–1.51)	NC	1.120 (0.67–2.85)

Note: Date are represented as geometric mean (% coefficient of variation geometric mean) unless otherwise stated.

Abbreviations: AUC, area under the plasma drug concentration–time curve, as defined from 0 h to the last time of quantifiable concentration (t), to 24 h, or extrapolated to infinity time (∞). CL/F, apparent clearance; C_max, maximum serum concentration; F, oral bioavailability; R_ac, accumulation ratio for AUC; R_cmax, accumulation ratio for C_max; T_max, time to maximum observed plasma drug concentration; t_1/2, terminal half‐life; V_z/F, apparent volume of distribution.

^a n = 6;

^b n = 7;

^c n = 5;

^d n = 2;

^e n = 4;

^f n = 1;

^g median and range presented;

^h at steady state; NC: not calculable.