| | |
Degree of hepatic impairment
| |
Degree of renal impairment
|
|---|
|
PK parameter
|
Normal hepatic function (n = 8)
|
Mild (n = 8)
|
Moderate (n = 8)
|
Severe (n = 8)
|
Normal renal function (n = 18)
|
Mild (n = 12)
|
Moderate (n = 9)
|
Severe (n = 9)
|
|---|
|
AUC(0-t) (ng·h/mL)*
|
5460 (46.2)
|
7560 (65.1)
|
7850 (50.3)
|
15100 (49.8)
|
5560 (36.9)
|
6910 (57.5)
|
9090 (35.2)
|
9640 (37.7)
|
|
AUC (ng·h/mL)*
|
5480 (46.0)
|
7680 (68.8)
|
7940 (50.7)
|
15900 (52.9)
|
5490 (39.0)$
|
6950 (58.3)
|
8710 (3.8)£
|
9750 (38.8)
|
|
Cmax (ng/mL)*
|
566 (25.6)
|
526 (22.3)
|
505 (23.0)
|
536 (30.2)
|
545 (22.7)
|
531 (28.8)
|
550 (9.9)
|
619 (20.6)
|
|
tmax (h)†
|
2 (1-2)
|
2 (1-4)
|
2 (1-6)
|
2 (1-4)
|
1 (1-3)
|
1 (1-4)
|
2 (1-8)
|
1 (1-3)
|
|
t1/2 (h)‡
|
9.3 (3.6)
|
13.0 (9.4)
|
14.6 (6.5)
|
24.8 (10.9)
|
10.8 (2.7)$
|
11.3 (4.0)
|
13.5 (4.3)£
|
13.2 (4.7)
|
|
CL/F (mL/min)‡
|
33.2 (15.6)
|
25.0 (12.1)
|
23.6 (14.2)
|
11.9 (7.3)
|
32.7 (14.2)$
|
27.9 (18.9)
|
20.1 (6.5)£
|
18.2 (6.5)
|
|
Vss/F (L)‡
|
19.0 (6.1)
|
19.8 (3.1)
|
21.2 (7.2)
|
21.9 (7.1)
|
22.6 (7.0)$
|
20.8 (5.8)
|
19.3 (2.0)£
|
17.8 (3.4)
|
|
Fu (%)‡
|
22.5 (7.5)
|
23.4 (4.0)
|
20.2 (4.8)
|
29.2 (9.4)
|
22.8 (6.2)
|
25.4 (6.7)
|
26.6 (2.9)
|
27.9 (5.3)
|
|
CLR (mL/min)‡
|
-
|
-
|
-
|
-
|
17.4 (13.9)$
|
10.3 (16.8)
|
3.2 (5.6)£
|
2.3 (2.7)£
|
|
Fe (%)‡
|
-
|
-
|
-
|
-
|
47.2 (18.0)
|
27.1 (19.5)
|
12.7 (16.9)
|
10.5 (9.0)£
|
|
Free Cmax (ng/mL)*
|
121 (58.7)
|
123 (21.9)
|
97.3 (32.4)
|
149.2 (52.6)
|
121 (32.3)
|
131 (22.9)
|
145 (13.4)
|
170 (18.2)
|
|
Free AUC (ng·h/mL)*
|
1170 (69.3)
|
1800 (54.7)
|
1460 (56.5)
|
4430 (40.0)
|
1230 (39.1)$
|
1720 (60.6)
|
2260 (34.5)£
|
2680 (38.9)
|
|
Unbound CL/F (mL/min)‡
|
167 (98.4)
|
103 (46.8)
|
129 (69.8)
|
40 (14.7)
|
146 (67.3)$
|
115 (83.8)
|
77.4 (24.1)£
|
65.8 (22.3)
|
- *Geometric mean (coefficient of variation, %), †median (range), ‡arithmetic mean (standard deviation), $n = 16, £n = 8. AUC(0-t), area under the plasma concentration-time curve from 0 to the time of the last quantifiable concentration; AUC, area under the plasma concentration-time curve from 0 to infinity; CL/F, total apparent drug clearance; CLR, renal clearance; Cmax, maximum plasma concentration; Fe, fraction of dose excreted unchanged; Fu, ratio of unbound drug in plasma; tmax, time to reach Cmax; t1/2, terminal half-life; Vss/F, volume of distribution at steady state.
