Abstract：
:Administration of the antiarrhythmic drug amiodarone to humans or animals may result in lung damage. Amiodarone is metabolized to desethylamiodarone and other minor metabolites. Because amiodarone and the metabolites accumulate in the lungs, it is not possible to ascertain the role of each of these compounds in the induction of toxicity. In the present study, we utilized primary cell cultures of rat alveolar macrophages to study the actions of amiodarone and desethylamiodarone individually and in combination. Neither drug species was metabolized by the cells over 42 h in culture thereby permitting assessment of the actions of each. Both drugs induced the formation of lamellar inclusions, indicative of the development of cellular phospholipidosis. Desethylamiodarone appeared to induce formation of the structures in a shorter period of time than did amiodarone, although given adequate exposure, the two drugs produced similar responses. At shorter times of exposure and lower concentrations, desethylamiodarone was more cytotoxic than amiodarone as assessed by the release of lactate dehydrogenase. The two in combination resulted in cytotoxicity that was more than additive. The results of this study indicate that in vitro cultures of alveolar macrophages may be quite useful in studying the role these cells play in the pulmonary toxicity associated with amiodarone therapy. Additionally, this study supports the idea that a significant portion of the toxicity may result from the actions of desethylamiodarone.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Ogle CL,Reasor MJdoi
10.1016/0300-483x(90)90112-tsubject
Has Abstractpub_date
1990-05-31 00:00:00pages
227-38issue
2eissn
0300-483Xissn
1879-3185pii
0300-483X(90)90112-Tjournal_volume
62pub_type
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