Distribution of amiodarone in heart tissues following intrapericardial administration.
The distribution of amiodarone (A) in heart tissues of open chest anesthetized animals was studied at 20 and 60 min following the insertion of an isotonic solution of the drug into the pericardial sac (PS) in doses from 0.25 to 3 mg per kg body weight (BW) for pigs and after 60 min in doses of 3 to 6 mg for dogs. Most of the A absorbed by the myocardium was found in the subepicardium part of the left ventricular (LV) wall. For both species the percentage of drug absorbed by the myocardium was largely and inversely related to the dose given, while uptake by the atria was positively related to the dose and was higher than that in the subepicardial LV wall. Sixty minutes after i.v. administration of A (3.0 mg per kg BW) the drug was evenly distributed across the LV wall (16 microg per g wet tissue), which was significantly lower (p < 0.02) than that of subepicardal LV wall (30 microg) after intrapericardial (IP) administration. This study shows that satisfactory drug concentrations in predicted and specific distribution in the heart tissue were derived shortly after intrapericardial administration without measurable circulation in the blood.
Department of Clinical Therapeutics, University of Athens, School of Medicine, Alexandra State and University Hospital, Greece.
J T
JT
Darsinos
J N
JN
Karli
E C
EC
Samouilidou
B
B
Krumbholz
A C
AC
Pistevos
G M
GM
Levis
D000638:Amiodarone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006328:Cardiac Catheterization; D004285:Dogs; D007275:Injections, Intravenous; D009206:Myocardium / Q000378:metabolism*; D010496:Pericardium; D013552:Swine; D014018:Tissue Distribution
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone