Phospholipidosis

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, rendering the cell unable to break down excess phospholipids. This is the currently favored view, resulting from drug-phospholipid complex formation.
 * 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.