Response of Rat Lungs to Amiodarone: Preferential Accumulation of Amiodarone and Desethylamiodarone in Alveolar Macrophages

Abstract

Treatment of humans with the antiarrhythmic drug amiodarone can cause pulmonary pathology and toxicity. The disorder is associated with the accumulation of phospholipid, amiodarone, and its principal metabolite desethylamiodarone in lung tissue. To better understand the response of the lung to amiodarone administration, the distribution of total phospholipid, amiodarone, and desethylamiodarone was determined in the lungs of male Fischer 344 rats as a function of treatment time with amiodarone. Rats were treated with amiodarone for 2 days, 1 week, or 9 weeks and the proportional accumulation of the three materials was measured in four fractions: (1) the residual lavaged lung, (2) the alveolar macrophage fraction, and (3) the sedimentable and (4) the nonsedimentable acellular lavage materials. The alveolar macrophage fraction demonstrated a preferential accumulation of phospholipid and both drugs. When isolated alveolar macrophages and type II cells were compared on a per cell basis, alveolar macrophages accumulated significantly more of the drugs and phospholipid throughout the treatment period. The results of this study illustrate the important role played by the alveolar macrophage in the sequestration of amiodarone and desethylamiodarone in rat lung.