Evaluation of the effects of PM101, a cyclodextrin-based formulation of intravenous amiodarone, on blood pressure in healthy humans. The American journal of cardiology [Am J Cardiol] Journal article

Title	Evaluation of the effects of PM101, a cyclodextrin-based formulation of intravenous amiodarone, on blood pressure in healthy humans.
Author(s)	Cushing DJ, Adams MP, Cooper WD, Zhang B, Lipicky RJ, Kowey PR
Institution	Prism Pharmaceuticals, King of Prussia, Pennsylvania, USA. dcushing@prismpharma.com
Source	Am J Cardiol 2009 Oct 15; 104(8):1152-7.
MeSH	Adolescent Adult Amiodarone Anti-Arrhythmia Agents Arrhythmias, Cardiac Blood Pressure Dose-Response Relationship, Drug Double-Blind Method Female Follow-Up Studies Heart Rate Humans Injections, Intravenous Male Middle Aged Prognosis Reference Values Young Adult beta-Cyclodextrins
Abstract	Intravenous amiodarone (AIV) is used to treat cardiac arrhythmias. Hypotension is the dose-limiting adverse event of AIV and is considered to be due to the cosolvents (polysorbate 80 and benzyl alcohol) in the formulation. To minimize hypotension, the initial loading dose of AIV (150 mg) is diluted to 1.5 mg/ml and slowly infused over 10 minutes. PM101 is a cosolvent-free intravenous formulation of amiodarone. The present study was designed to assess any potential hypotensive effect of PM101 (50 mg/ml) on the administration of the loading dose (150 mg) as an undiluted bolus push. This was a randomized, double-blind, placebo- and active-controlled study in healthy human subjects receiving placebo (5% dextrose in water, n = 112) or PM101 (bolus push, n = 112). The primary end point was the noninferiority assessment of placebo versus PM101 for change in systolic blood pressure. For comparison, the standard loading dose of AIV (150 mg) was infused at 1.5 mg/ml over 10 minutes, and a rapid loading dose of AIV (150 mg) was infused undiluted (50 mg/ml) over 15 seconds. PM101 was noninferior to placebo, with changes from baseline systolic blood pressure for placebo and PM101 of -4.25 +/- 4.2 and -4.83 +/- 5.0 mm Hg, respectively. Neither regimen of AIV altered systolic blood pressure compared to placebo. Transient and significant increases in heart rate were observed in both AIV groups and with PM101 but not placebo. In conclusion, the results of this study demonstrate that PM101 is devoid of hypotension in healthy human subjects. The absence of a hypotensive effect of AIV in this population suggests that further evaluation is needed in a patient population with cardiac disease.
Language	eng
Pub Type(s)	Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't
PubMed ID	19801040

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