DIPL has become a significant concern for drug development and safety assessment because its association with drug toxicity is unclear. For example, DIPL in animals is described in the drug labeling for azithromycin (Zithromax), telithromycin (Ketek), and fluoxetine (Prozac). The significance and prevalence of DIPL for humans remains unclear.
Drugs that cause DIPL in animals and humans are associated with unwanted clinical side effects, such as drug-induced QT prolongation, myopathy, hepatotoxicity, nephrotoxicity, or pulmonary dysfunction. For example, drugs with the potential to cause QT prolongation, including macrolide antibiotics (telithromycin, erythromycin), antiarrthymic drug (amiodarone), antidepressants (imipramine, fluoxetine) and antipsychotic drugs (haloperidol, chlorpromazine), also cause phospholipidosis in animal and human tissues. A number of anti-malarial compounds (chloroquine, hydroxychloroquine, mefloquine, quinine, quinidine) cause phospholipidosis, myopathy and neurological damage. DIPL of the kidney proximal tubules and glomerular podocytes occurs frequently with the development of the renal toxicities of aminoglycosides (gentamicin, tobramycin, netilmicin, and amikacin) and chloroquine, respectively. The similarities between DIPL and the inherited lysosomal storage disorder Niemann-Pick disease type C also present an issue for regulators.
Read more about this topic: Phospholipidosis