Table 3.

Steady-state non-compartmental pharmacokinetic parameters of linagliptin after multiple oral doses of 5 mg linagliptin in patients with mild or moderate hepatic impairment compared with healthy subjects

Hepatic impairment group
	Healthy (n = 8)		Mild (n = 8)		Moderate (n = 8§)
	gMean	gCV	gMean	gCV	gMean	gCV
AUCτ,ss (nmol l−1 h)	254	18.9	191	27.2	217	26.0
Cmax,ss (nmol l−1)	20.8	38.6	13.4	55.8	19.2	52.5
tmax,ss (h)*	1.50	0.50–2.00	1.00	0.50–3.00	0.625	0.25–2.00
C24,ss (nmol l−1)	8.41	18.2	6.75	28.2	7.85	18.8
t1/2,ss (h)	77.7	32.6	95.0	18.0	96.1	54.7
fe(0,24 h),ss (%)	7.12	50.3	4.84†	57.8	6.13	51.2
CLR,(0,24 h),ss (ml min−1)	49.5	40.8	44.7†	40.1	49.8	50.8
RA,AUC(0,24 h)	1.34	22.2	1.25‡	23.9	1.46	28.4
	1.20	53.9	1.22‡	64.3	1.53	65.8
Accumulation t1/2 (h)	10.9	66.2	8.11‡	86.8	13.1	61.7

^*For t_max, the median and range (min–max) is given.

^†Urine linagliptin concentrations only available for whole of day 1 for seven patients in the mild impairment group.

^‡Single dose and steady-state pharmacokinetic data only available for seven patients in the mild impairment group.

^§Eight patients only completed full 7 days of study in the moderate impairment group. AUC_τ,ss area under the plasma concentration–time curve at steady-state over the dosing interval τ, C_max,ss maximum plasma concentration at steady-state, t_max,ss time from last dosing to maximum plasma concentration at steady-state over the dosing interval τ, C_24,ss plasma concentration at 24 h at steady-state, t_1/2,ss terminal half-life in plasma at steady-state, fe(0,24 h)_,ss fraction excreted unchanged in urine in the time interval 0 to 24 h at steady-state; CL_R(0,24 h)_,ss renal clearance in the time interval 0 to 24 h at steady-state, R_{A,AUC(0,24 h)} accumulation ratio based on AUC(0,24 h), accumulation ratio based on C_max, Accumulation t_1/2 equals t× ln(2)/ln(R_{A,AUC(0,24 h)}/[R_{A,AUC(0,24 h)}– 1]).