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 |
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|
Child A |
Child C |
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| 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.
a
P < 0.01,
c
P < 0.001 vs placebo;
b
P < 0.05 vs healthy subjects and patients with Child grade A cirrhosis;
d
P < 0.001 vs healthy subjects and P < 0.05 vs patients with Child grade A cirrhosis;
f
P < 0.001 vs healthy subjects and patients with Child grade A cirrhosis. CL: Systemic clearance; CLf: Formation clearance; CLu: Unbound systemic clearance; CLuf: Unbound formation clearance; Css: Steady-state trough concentration (μg/mL).