Pharmacokinetic parameters (mean ± S.D., range in parentheses) of amiodarone and desethylamiodarone after i.v. and oral administration in rats in the absence (controls) and presence of oral ketoconazole (17.1 mg/kg, three doses over 1 day)
Intravenous (25 mg/kg AM HCl) | Oral (50 mg/kg AM HCl) | ||||
|---|---|---|---|---|---|
| Control (n = 6) | KTZ (n = 6) | Control (n = 5) | KTZ (n = 5) | ||
| Amiodarone | |||||
| AUC0-48 h (mg · h/l) | |||||
| 15.4 ± 2.90 | 25.6 ± 6.02a | 8.73 ± 1.98 | 26.8 ± 9.03a | ||
| (12.6-19.5) | (20.6-34.1) | (7.06-12.0) | (17.7-36.8) | ||
| AUC0-∞ (mg · h/l) | |||||
| 18.5 ± 3.27 | 29.6 ± 7.49a | 13.6 ± 6.97 | 28.0 ± 9.46a | ||
| (13.4-23.0) | (22.2-41.5) | (8.11-24.1) | (18.3-39.3) | ||
| CL (ml/h/kg) | |||||
| 1390 ± 269 | 889 ± 209a | ||||
| (1086-1860) | (602-1126) | ||||
| Vdss (l/kg) | |||||
| 40.9 ± 19.7 | 20.2 ± 9.47a | ||||
| (22.1-51.5) | (9.01-37.0) | ||||
| t1/2 (h) | |||||
| 39.4 ± 24.2 | 30.1 ± 21.5 | 32.2 ± 21.9 | 9.93 ± 1.31 | ||
| (17.2-78.8) | (10.1-59.5) | (16.9-69.8) | (8.21-11.3) | ||
| Cmax (ng/ml) | 723 ± 355 | 1716 ± 495a | |||
| (317-1123) | (1329-2296) | ||||
| Median tmax (h) | 5.93 | 8.00 | |||
| (2.18-10.1) | (2.08-10.3) | ||||
| Desethylamiodarone | |||||
| Cmax (ng/ml) | |||||
| 66.2 ± 50.0 | 86.1 ± 55.1 | 49.1 ± 29.5 | 138 ± 93.3 | ||
| Median tmax (h) | |||||
| 0.369 | 24.4 | 5.93 | 10.0 | ||
| (0.083-3.7) | (0.116-49.3) | (3.21-10.2) | (6.06-10.5) | ||
↵ a Significantly different from similarly dosed control rats.