Table 2.

Main pharmacokinetic parameters after multiple dose administration of BAF312 to healthy subjects under fasted conditions over 28 days

Pharmacokinetic parameterA	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
	0.3 mg·day−1	1 mg·day−1	2.5 mg·day−1	10 mg·day−1	20 mg·day−1
Day 1
N	n= 6	n= 6	n= 7	n= 9	n= 9
Tmax (h)B	3.00 (3.00–6.00)	4.50 (2.00–8.00)	3.00 (3.00–6.00)	3.00 (2.00–6.00)	4.00 (3.00–8.00)
Cmax (ng·mL−1)C	2.13 [13]	8.01 [6]	17.4 [88]	84.1 [11]	162 [20]
AUC0–24 h (h*ng·mL−1)D	36.2 [10]	136 [8]	293 [85]	1370 [11]	2740 [14]
Day 28
n	n= 6	n= 6	n= 5	n= 9	n= 8
Tmax,ss (h)B	3.50 (3.00–12.00)	3.00 (2.00–8.00)	4.00 (3.00–8.00)	3.00 (2.00–6.00)	3.00 (3.00–4.00)
Cmax,ss (ng·mL−1)C	5.31 [16]	14.9 [10]	38.3 [37]	147 [24]	359 [17]
AUCτ (h*ng·mL−1)C	97.9 [19]	282 [16]	692 [45]	2580 [24]	6370 [23]
Cavg, ss (ng·mL−1)C	4.08 [19]	11.7 [16]	28.8 [45]	107 [24]	265 [23]
Cmin,ss (ng·mL−1)C	2.83 [27]	7.74 [20]	15.2 [120]	70.6 [29]	166 (88.0)D
Effective T1/2(h)C,E	36.2 [19]	25.2 [12]	36.3 [47]	21.9 [19]	28.8 [23]
RaccC	2.71 [19]	2.07 [12]	2.72 [47]	1.88 [19]	2.28 [23]

^AAbbreviations and definitions for pharmacokinetic parameters: T_max,ss: the time to reach maximum (peak) concentration following drug administration at steady state; C_max,ss: the maximum (peak) observed steady-state drug concentration in the plasma during multiple dosing; AUC_τ: area under curve during a dosing interval (τ) at steady state; C_avg,ss: the mean observed steady-state drug concentration in the plasma during multiple dosing; C_min,ss: minimum (trough) observed steady-state drug concentration in the plasma during multiple dosing; T_1/2: elimination half-life associated with the terminal slope (λ_z) of a semilogarithmic concentration-time curve; R_acc: accumulation ratio.

^BMedian (min-max).

^CGeometric mean [%CV geo mean].

^DArithmetic mean (SD).

^EEffective elimination half-life based on drug accumulation at steady-state (Boxenbaum and Battle, 1995).