Phospholipidosis

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Phospholipidosis is a lipid storage disorder in which excess phospholipids accumulate within cells. Drug-induced phospholipidosis is an adverse drug reaction that occurs with many cationic amphiphillic drugs. While the mechanism is not truly understood, four possible mechanisms have been proposed, outlined below:

The drug may inhibit phospholipases due to binding to the substrate phospholipid, rendering the cell unable to break down phospholipids. This is the currently favored view, supported by e.g. the recent demonstration of a very strong correlation between phospholipidosis and the strength of drug-phospholipid interaction (see Vitovic et al., J.Med.Chem. 51, 1842-1848, 2008).
Increased synthesis of phospholipids within the cell.
Binding of the drug to phospholipids, preventing phospholipases from breaking down these drug-phospholipid complexes: a build-up of phospholipids bound to the drug yields results similar to a drug depot, with the possibility of decreased metabolism of drug and a later increase in exposure as the drug is released from the depot, or a disruption in cell function due to increased cytoplasmic space occupied through phospholid accumulation.
Breakdown of the lipids by the drug inducing lipid biosynthesis (See Baciu et al. 2006} .

A major concern for drug regulatory agencies is drug-induced phospholipidosis occurring in hepatocytes, kidneys, and lungs, which causes failure of liver, kidney, and respiratory function.