Drug-induced phospholipidosis: issues and future directions

Expert Opin Drug Saf. 2006 Jul;5(4):567-83. doi: 10.1517/14740338.5.4.567.


Numerous drugs containing a cationic amphiphilic structure are capable of inducing phospholipidosis in cells under conditions of in vivo administration or ex vivo incubation. The principal characteristics of this condition include the reversible accumulation of polar phospholipids in association with the development of unicentric or multicentric lamellated bodies within cells. There is an abundance of data providing an understanding of potential mechanisms for the induction of phospholipidosis; however, the process is likely to be complex and may differ from one drug to another. The functional consequences of the presence of this condition on cellular or tissue function are not well understood. The general consensus is that the condition is an adaptive response rather than a toxicological manifestation; however, additional studies to examine this question are needed. Until this issue is resolved, concerns about phospholipidosis will continue to exist at regulatory agencies. Procedures for the screening of potential phospholipogenic candidate compounds are available. In contrast, a clear need exists for the identification of valid biomarkers to assess the development of phospholipidosis in preclinical and clinical studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / toxicity*
  • Drug Evaluation, Preclinical
  • Histamine H1 Antagonists / chemistry
  • Histamine H1 Antagonists / toxicity*
  • Humans
  • Lipidoses / etiology*
  • Lipidoses / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Lung / drug effects
  • Lung / enzymology
  • Lysosomes / drug effects
  • Lysosomes / enzymology
  • Molecular Structure
  • Phospholipids / metabolism*
  • Serotonin Uptake Inhibitors / chemistry
  • Serotonin Uptake Inhibitors / toxicity*


  • Anti-Bacterial Agents
  • Histamine H1 Antagonists
  • Phospholipids
  • Serotonin Uptake Inhibitors