Table 3.

Pharmacokinetic parameters of BI 853520 after single- and multiple-dose administration in cycle 1 (200 mg once daily cohort)

Parameter	BI 853520 200 mg QD
	Geometric mean	Geometric CV, %
Single dose (N = 15)
AUCτ,1, nmol·h/L	15,300	50.6
AUC0−∞, nmol·h/L	26,300	55.6
Cmax, nmol/L	1570	40.7
tmax, ha	2.00	1.00–3.00
t½, h	20.9	29.9
MRTpo, h	28.0	30.2
CL/F, mL/min	216	55.6
Vz/F, L	391	53.1
fe0–24,  %	5.60b	33.9b
CLR,0−24, mL/min	21.7b	47.7b
Multiple dose (N = 10)
AUCτ,ss, nmol·h/L	36,800	94.6
Cmax,ss, nmol/L	2750	77.3
tmax,ss, ha	2.94	1.00–7.93
t½,ss, h	20.3c	24.9c
MRTpo,ss, h	28.3c	23.2c
CL/F,ss, mL/min	155	94.6
Vz/F,ss, L	311c	87.1c
RA,AUC	2.15	58.4
$R_{\mathrm{A},C_{max}}$	1.62	56.9
fe0−24,ss,  %	8.86	30.3
CLR,0–24,ss, mL/min	13.7	71.1

AUC_τ,1 area under the plamsa concentration–time curve over a uniform dosing interval τ after administration of the first dose, AUC_τ,ss area under the plasma concentration-time curve at steady state over a uniform dosing interval τ, AUC_0−∞ area under the plasma concentration–time curve extrapolated from time zero to infinity, CL/F apparent clearance, CL/F_ss apparent clearance at steady state, CL_R,0–24 renal clearance from time zero to 24 h, CL_R,0–24,ss renal clearance from time zero to 24 h at steady state, C_max maximum plasma concentration, C_max,ss maximum plasma concentration at steady state, CV coefficient of variation, fe_0–24 fraction excreted in urine from time zero to 24 h, fe_0–24,ss fraction excreted in urine from time zero to 24 h at steady state, MRT_po mean residence time following oral administration, MRT_po,ss mean residence time following oral administration at steady state, QD once daily, R_A,AUC accumulation ratio over the dosing interval τ at steady state, expressed as ratio of AUC at steady state and after single dose, R_A,Cmax accumulation ratio over the dosing interval τ at steady state, expressed as ratio of C_max at steady state and after single dose, t_½ terminal half-life, t_max time to maximum plasma concentration, V_Z/F apparent volume of distribution, V_Z/F_ss apparent volume of distribution at steady state

^aShown as median and range

^bData available for 13 patients

^cData available for nine patients