Population pharmacokinetics of intravenous amiodarone in patients with refractory ventricular tachycardia/fibrillation

A population approach was used to determine the pharmacokinetics of amiodarone in 245 patients receiving intravenous amiodarone for the short-term treatment of refractory, hemodynamically destabilizing, ventricular tachycardia and/or fibrillation. A two-compartment model employing proportional statistical models to estimate intersubject variability and an additive-proportional model to estimate residual error were found to best describe the data. The mean (% coefficient of variation, CV) value for clearance was 0.22 L/hr/kg (13%), central volume of distribution was 0.30 L/kg (11%), peripheral volume of distribution was 10.0 L/kg (9.5%), and intercompartmental clearance was 0.71 L/hr/kg (16%). The mean (%CV) intersubject variance estimates were 1.52 (31%) for clearance, 0.37 (46%) for central volume, 0.37 (67%) for peripheral volume, and 0.44 (39%) for intercompartmental clearance. The estimate of residual error (%CV) was 0.53 (13%). Age, gender, height, serum creatinine concentration, serum alkaline phosphatase activity, ejection fraction, and therapeutic response to treatment did not contribute to the variability in patient pharmacokinetics. It was concluded that the pharmacokinetic parameters of amiodarone in these patients were similar to those reported for healthy volunteers and were similarly variable. Estimates of pharmacokinetic parameters made during short periods of observation may not be entirely consistent with parameters estimated during prolonged periods of observation of healthy volunteers who receive single doses.
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