Bioequivalence of 2 intravenous amiodarone formulations in healthy participants.
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-infinity). 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.
Cushing
Daniel J
DJ
Prism Pharmaceuticals, Inc, 1150 First Avenue, Suite 1050, King of Prussia, PA 19406, USA. dcushing@prismpharma.com
Adams
Michael P
MP
Cooper
Warren D
WD
Kowey
Peter R
PR
Lipicky
Raymond J
RJ
D000293:Adolescent; D000328:Adult; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
D000889:Anti-Arrhythmia Agents; D003505:Cyclodextrins; D000638:Amiodarone