Skip to main content

Table 3 Pharmacokinetic parameters of zibotentan in subjects with normal renal function and varying degrees of renal impairment, normal hepatic function and varying degrees of hepatic impairment

From: Pharmacokinetics and tolerability of zibotentan (ZD4054) in subjects with hepatic or renal impairment: two open-label comparative studies

   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)
  1. *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.