D. Cushing, M. Adams, W. D. Cooper
Apr 1, 2009
Citations
0
Influential Citations
15
Citations
Quality indicators
Journal
The Journal of Clinical Pharmacology
Abstract
Intravenous amiodarone is an effective agent for the treatment of recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia. PM101 is a new formulation of intravenous amiodarone that uses a cyclodextrin to maintain amiodarone in the aqueous phase. Eighty‐eight participants were enrolled in this randomized, double‐blind, crossover, bioequivalence clinical study and were treated with single doses (150 mg) of PM101 and intravenous amiodarone separated by a washout period of at least 42 days. Venous blood samples were taken periodically during the first 72 hours after dosing to determine standard pharmacokinetic parameters. The amiodarone plasma concentration‐time curve observed with both formulations was virtually identical, as was the 72‐hour area under the curve (AUC0–72). Similar equivalence was seen for desethylamiodarone, the active metabolite of amiodarone. The geometric ratios of the AUC0–72 for amiodarone and desethylamiodarone were 1.03 (95% confidence interval [CI], 1.00–1.06) and 1.01 (0.99–1.03), respectively. Similar geometric ratios and CIs were found for maximum plasma concentration (Cmax) and for AUC extrapolated to infinity (AUC0‐∞). Because the ratios and their CI fell between the limits of 0.8 and 1.25, bioequivalence of these 2 formulations was established. No safety concerns unique to PM101 were identified.