Pharmacokinetic drug interactions in liver disease: An update

Table 2 Effect of erythromycin on the pharmacokinetic parameters of quinine and 3-hydroxyquinine in healthy subjects and cirrhotic patients

Parameter	Healthy subjects		Patients with cirrhosis
			Child A		Child C
	Placebo	Erythromycin	Placebo	Erythromycin	Placebo	Erythromycin
CL quinine	1.775 ± 0.310	1.161 ± 0.309a	1.504 ± 0.362	1.040 ± 0.303a	1.281 ± 0.394b	1.401 ± 0.534
Inhibition (%)	33 (27-38)		30 (26-34)		-7 (-16-2)f
CLf 3-hydroxiquinine	0.174 ± 0.051	0.059 ± 0.017c	0.140 ± 0.077	0.056 ± 0.032c	0.085 ± 0.028d	0.037 ± 0.023c
Inhibition (%)	65 (61-70)		61 (56-67)		59 (46-72)
Unbound quinine (%)	6.7 ± 0.8	9.4 ± 1.0c	7.1 ± 1.6	10.3 ± 2.8c	11.9 ± 3.7f	19.9 ± 5.5cf
Increase (%)	41 (28-55)		45 (33-55)		76 (42-111)b
CLu quinine	26.81 ± 11.49	12.30 ± 3.16c	21.18 ± 8.45	10.10 ± 3.88c	10.95 ± 2.19f	7.24 ± 2.77bc
Inhibition (%)	51 (44-59)		50 (45-55)		35 (21-48)b
CLuf 3-hydroxiquinine	2.63 ± 0.88	0.64 ± 0.20c	1.97 ± 1.09	0.55 ± 0.31c	7.01 ± 3.33f	4.06 ± 2.58ad
Inhibition (%)	75 (70-80)		73 (70-77)		74 (64-84)
Erythromycin Css		1.33 ± 0.25		1.18 ± 0.44		1.85 ± 1.00

Data are taken or calculated from Orlando et al[47]; all clearance values are expressed as mL/min per kg; inhibition or increase values are given as means with 95% confidence limits.

^aP < 0.01,

^cP < 0.001 vs placebo;

^bP < 0.05 vs healthy subjects and patients with Child grade A cirrhosis;

^dP < 0.001 vs healthy subjects and P < 0.05 vs patients with Child grade A cirrhosis;

^fP < 0.001 vs healthy subjects and patients with Child grade A cirrhosis. CL: Systemic clearance; CL_f: Formation clearance; CL_u: Unbound systemic clearance; CL_uf: Unbound formation clearance; C_ss: Steady-state trough concentration (μg/mL).