Influence of a pre-existing phospholipidosis on the accumulation of amiodarone and desethylamiodarone in rat alveolar macrophages.
Amiodarone is an antiarrhythmic drug that concentrates in the lungs and can cause pulmonary damage in humans. The purpose of the present study was to examine the influence of a pre-existing lung pathology on the pulmonary accumulation of amiodarone and its primary metabolite, desethylamiodarone. To study this problem, male Fischer 344 rats were administered chlorphentermine to induce a phospholipidosis in the alveolar macrophages of the lungs. The accumulation of amiodarone and desethylamiodarone in phospholipidotic alveolar macrophages was measured following 5 weeks of amiodarone administration. When calculated on a per cell basis, the levels of both drugs were increased over 10-fold in phospholipid-laden macrophages compared to cells from control rats in which a phospholipidosis was not present. When phospholipidotic macrophages were exposed to amiodarone and desethylamiodarone in vitro, both drugs were accumulated to a higher level than occurred in cells from control rats. The results of this study demonstrate that the presence of a pre-existing phospholipidosis results in an enhanced accumulation of amiodarone and desethylamiodarone in rat alveolar macrophages.
Reasor
M J
MJ
Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown 26506.
D000638:Amiodarone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002745:Chlorphentermine; D008064:Lipidoses / Q000139:chemically induced / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D010743:Phospholipids; C036116:desethylamiodarone; D000638:Amiodarone; D002745:Chlorphentermine