Pharmacokinetic Disposition of Amiodarone When Given with an Intralipid Rescue Strategy.

Sean N Avedissian,Michelle Pham,Cristina Miglis,Ashkan Salamatipour,Jeffin M Panickar,Medha D Joshi,Khrystyna Hlukhenka,Theodoros Xanthos,Marc H Scheetz,Athanasios Chalkias

doi:10.3390/pharmaceutics13040539

Abstract

While the antiarrhythmic drug amiodarone is commonly used in clinical practice, it has a narrow therapeutic index that can lead to acute overdose. One proposed method to deal with this toxicity is lipid emulsion therapy, which may potentially quench the free amiodarone in blood and prevent its further distribution to target organs and tissues. In this study, we utilize an established swine model to examine the effects of Intralipid™ (IL) administration for acute amiodarone toxicity. A total of 14 pigs received an overdose of intravenous amiodarone. After twenty minutes, half of the pigs (n = 7) received IL while the control group (n = 7) received normal saline. Serum concentrations of amiodarone were then analyzed using a validated high-performance liquid chromatography (HPLC) method. Noncompartmental pharmacokinetic analyses were performed on the observed concentrations. There were no statistical differences in the area under the concentration time curve (6 h) or clearance, but there was a difference in the half-life between the two groups (3.12 vs. 0.85 h, p = 0.01). The administration of IL did not statistically change the overall exposure of amiodarone in the blood in the first 6 h; however, trends toward prolonged blood retention in the IL group were seen.

Highlights

Amiodarone is a highly effective antiarrhythmic agent used to treat a variety of supraventricular and ventricular cardiac arrhythmias [1]
It has been reported that amiodarone is mainly metabolized to desethylamiodarone by the cytochrome P450 isoenzyme; this conversion is minimal when it is given as an acute intravenous infusion
No significant interfering peaks from endogenous substances in blank serum were observed in drug-free porcine serum at the retention time of the analyte and the internal standard

Summary

Introduction

Amiodarone is a highly effective antiarrhythmic agent used to treat a variety of supraventricular and ventricular cardiac arrhythmias [1]. Amiodarone’s adverse effects can be divided into two categories: those which occur during the intravenous loading dose and those associated with chronic oral administration [3]. It has been reported that amiodarone is mainly metabolized to desethylamiodarone by the cytochrome P450 isoenzyme; this conversion is minimal when it is given as an acute intravenous infusion. For this reason, amiodarone toxicity associated with intravenous use is thought to be caused primarily by the parent compound [8]. While intravenous amiodarone has been shown to cause hypotension in humans and swine, limited clinical data exist on the treatment of acute toxicity [5,11]

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Discussion

Conclusion