Time course of myocardial amiodarone uptake in the piglet heart using a chronic animal model.
This investigation sought to study single dose pharmacokinetics of amiodarone in a chronic animal model. We developed a new chronic animal model that allows serial direct access to the heart of the immature piglet via an implanted acrylic thoracic window. Following instrumentation and 72-hour recovery, amiodarone (5 mg/kg) was administered as a single intravenous bolus in immature piglets. Timed paired serum samples and myocardial biopsies for amiodarone level were obtained prior to, and up to 72 hours following, amiodarone administration. Peak concentrations of amiodarone in both serum (3.60 +/- 1.02 micrograms/ml) and tissue (84.2 +/- 6.50 ng/mg) occurred within 5 minutes of drug administration. As reported by others, this study demonstrated that the volume of distribution (VD) of amiodarone was large (33.31 +/- 35.21 L/kg), and the clearance (Cl) was low (13.6 +/- 4.4 ml/min/kg). Marked prolongation of both the serum t1/2 (29.98 +/- 29.26 hours) and the myocardial t1/2 (29.20 +/- 29.49 hours) were noted as well. The early, rapid myocardial peak of amiodarone in the immature myocardium corresponds with recent clinical observations of onset of antiarrhythmic efficacy 5 to 10 minutes following intravenous amiodarone administration in young children.
Beder
S D
SD
Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Childrens Hospital, Cleveland, OH, USA.
Cohen
M H
MH
BenShachar
G
G
D000638:Amiodarone / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone