Martin W J, Standing J E
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
J Pharmacol Exp Ther. 1988 Feb;244(2):774-9.
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.
胺碘酮肺毒性是一种危及生命的药物不良反应。我们的研究通过支气管肺泡灌洗（BAL）检查了10例胺碘酮肺毒性患者，并确定与对照受试者（n = 7）相比，BAL获取的细胞中各种磷脂显著增加。双单酰甘油磷酸酯和磷脂酰甘油的相对量和绝对量均显著增加（P小于0.01）。细胞组分中其他几种磷脂的绝对量也显著增加。相比之下，无细胞BAL液中磷脂含量仅显示出微小差异。BAL细胞中胺碘酮及其主要代谢产物去乙基胺碘酮的浓度之间存在很强的直接相关性（r = 0.98），并且胺碘酮或去乙基胺碘酮的浓度与细胞中磷脂的积累之间也存在直接相关性（r = 0.97，两种测定结果）。这项研究表明，人体受试者BAL的结果可能为肺磷脂沉积症提供具体且可量化的证据，并表明BAL细胞中药物或其主要代谢产物的浓度是肺中磷脂积累程度的主要决定因素。
