Table 3. Pharmacokinetic profile of EZN-4176.

	t1/2	Cmax	AUC0–72	AUC0–t	AUC0–∞	Cl	Vss
Cohort	(h)	(ng ml−1)	(h ng ml−1)	(hr ng ml−1)	(hr ng ml−1)	(ml hr−1 kg−1)	(ml kg−1)
Cohort A 0.5 mg kg−1
Mean	54.8	4540	8060	8110	8180	61.3	296
s.d.	33.7	1340	622	558	518	3.83	275
CV%	61.5	29.6	7.71	6.88	6.33	6.25	92.7
Cohort B 1 mg kg−1
Mean	82.5	5600	12 300	12 400	12 500	82.1	518
s.d.	70.1	1190	2420	2430	2390	17.6	369
CV%	85	21.3	19.7	19.6	19.1	21.4	71.2
Cohort C 2 mg kg−1
Mean	221	11 300	30 700	31 000	32 300	63.8	1820
s.d.	126	1490	6420	6490	6270	13.9	1620
CV%	57.3	13.2	20.9	20.9	19.4	21.8	89.1
Cohort D 4 mg kg−1
Mean	63.6	26 900	83 300	84 000	84 600	49.3	281
s.d.	13.8	6820	21 900	22 100	22 400	11.6	56.1
CV%	21.7	25.4	26.3	26.3	26.5	23.5	20
Cohort E 6.5 mg kg−1
Mean	55.8	44 100	151 000	151 000	152 000	48.8	244
s.d.	20.4	12 000	69 200	69 200	69 300	20.5	103
CV%	36.6	27.2	45.9	45.7	45.6	42	42.4
Cohort F 10 mg kg−1
Mean	86.2	97 300	409 000	411 000	413 000	33.9	249
s.d.	32.9	61 800	299 000	299 000	299 000	17.5	181
CV%	38.2	63.5	73	72.7	72.3	51.8	72.9

Abbreviations: AUC_0–t=area under the drug concentration–time curve (AUC) from time zero to time t, where t is the time of the last measurable concentration (C_t); AUC_0–∞=AUC from time zero to infinity; Cl=plasma clearance (dose/AUC_0-∞); C_max=maximum observed drug concentration; CV=coefficient of variation; t_last=time of last measurable drug concentration; t_max=time of maximum drug concentration (obtained without interpolation); V_ss=apparent volume of distribution at steady-state.