Amiodarone pulmonary toxicity: biochemical evidence for a cellular phospholipidosis in the bronchoalveolar lavage of human subjects

Abstract

Amiodarone pulmonary toxicity represents an example of a life-threatening adverse drug reaction. Our study examined 10 subjects with amiodarone pulmonary toxicity by bronchoalveolar lavage (BAL) and determined that cells obtained by BAL demonstrated marked increases in various phospholipids compared to control subjects (n = 7). Bis monoacylglycerol phosphate and phosphatidylglycerol were significantly increased in both relative and absolute amounts (P less than .01). Several other phospholipids also were significantly increased in absolute amounts within the cell fraction. In contrast, the cell-free BAL fluid revealed only minor differences in phospholipid content. There was a strong direct correlation between concentration of amiodarone and its primary metabolite, desethylamiodarone in BAL cells (r = 0.98), and also a direct correlation between either the concentration of amiodarone or desethylamiodarone and the accumulation of phospholipids in the cells (r = 0.97, both determinations). This study indicates that findings from BAL in human subjects may provide specific and quantifiable evidence of pulmonary phospholipidosis, and suggests the concentration of the drug or its primary metabolite in BAL cells is a major determinant for the degree of phospholipid accumulation in the lung.