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HERO ID
1305797
Reference Type
Journal Article
Title
Amiodarone-induced pulmonary inflammation. Correlation with drug dose and lung levels of drug, metabolite, and phospholipid
Author(s)
Wilson, BD; Clarkson, CE; Lippmann, ML
Year
1991
Is Peer Reviewed?
Yes
Journal
American Review of Respiratory Disease
ISSN:
0003-0805
Volume
143
Issue
5 Pt 1
Page Numbers
1110-1114
Language
English
PMID
2024822
Abstract
To investigate the hypotheses that amiodarone-induced pulmonary inflammation may be related to direct drug toxicity, groups of 10 or more Wistar rats were fed amiodarone by gavage at concentrations of 175, 300, 400, and 500 mg/kg/day, or vehicle alone. After 6 wk of drug feeding, the rats were examined for histologic and cellular evidence of pulmonary inflammation. In addition, the amounts of amiodarone, the major metabolite of amiodarone N-desethylamiodarone (N-des), and phospholipid in the lungs were determined. We found that rats fed 175 mg/kg of amiodarone were essentially no different from control animals. The 175 mg/kg group had normal lung histologies, no change in lavage cell counts or differential counts, and very little amiodarone, N-des, or phospholipid in the lungs. In contrast, the three high-dose groups had abnormal lung histologies along with increases in lavage cell counts and change in differential counts. There were also significant increases in the amounts of amiodarone, N-des, and phospholipid in the lung. We conclude that the development of amiodarone-induced pulmonary inflammation is dose dependent, and that there is a direct correlation between the amount of amiodarone, N-des, and phospholipid in the lung with the development of inflammation. It therefore appears that the drug is directly toxic to lung tissue.
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