Pulmonary changes induced by amphophilic drugs.

Administration of amphophilic drugs to experimental animals causes formation of myeloid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli, and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myeloid bodies. In summary, administration of amphophilic compounds causes a drug-induced lysosomal disease or generalized phospholipidosis.