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

Table 4 Ratios of pharmacokinetic parameters of zibotentan in subjects with varying degrees of renal impairment compared with subjects with normal renal function, and in subjects with varying degrees of hepatic impairment compared with subjects with normal hepatic function

	Degree of hepatic impairment*			Degree of renal impairment^†
PK parameter	Mild	Moderate	Severe	Mild	Moderate	Severe
C_max ratio (90% CI)	0.93 (0.75-1.15)	0.89 (0.72-1.10)	0.95 (0.77-1.17)	1.07 (0.97-1.19)	1.09 (0.96-1.24)	1.12 (0.96-1.30)
AUC ratio (90% CI)	1.40 (0.91-2.17)	1.45 (0.94-2.24)	2.90 (1.88-4.49)	1.66 (1.38-1.99)	1.89 (1.50-2.39)	2.17 (1.64-2.86)
t_1/2 difference, h (90% CI)	-	-	-	1.87 (0.06-3.68)**	2.37 (0.08-4.66)**	2.87 (0.1-5.64)**

*Point estimate of geometric mean ratio in relation to control; ^†Point estimate of geometric least squares ratio in relation to control; **Least squares mean difference in relation to control; AUC, area under the plasma concentration-time curve from zero to infinity; C_max, maximum plasma concentration; t_1/2, terminal half-life; CI = confidence interval.