title: Influence of a pre-existing phospholipidosis on the accumulation of amiodarone and desethylamiodarone in rat alveolar macrophages.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown 26506.
authors.forename: M J
authors.initials: MJ
authors.lastname: Reasor
mesh_terms: 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
chemical_list: D010743:Phospholipids; C036116:desethylamiodarone; D000638:Amiodarone; D002745:Chlorphentermine