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Experimental Biology and Medicine 226:825-830 (2001)
© 2001 Society for Experimental Biology and Medicine

MINIREVIEW

Drug-Induced Phospholipidosis: Are There Functional Consequences?

Mark J. Reasor*,1 and Sam Kacew{dagger}

* Department of Physiology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 26506; and
{dagger} Department of Cellular and Molecular Medicine, University of Ottawa, School of Medicine, Ottawa, Ontario K1H8M5, Canada

Phospholipidosis induced by drugs with a cationic amphiphilic structure is a generalized condition in humans and animals that is characterized by an intracellular accumulation of phospholipids and the concurrent development of concentric lamellar bodies. The primary mechanism responsible for the development of phospholipidosis is an inhibition of lysosomal phospholipase activity by the drugs. While the biochemical and ultrastructural features of the condition have been well characterized, much less effort has been directed toward understanding whether the condition has adverse effects on the organism. While there are a few cationic amphiphilic drugs that have been reported to cause phospholipidosis in humans, the principal concern with this condition is in the pharmaceutical industry during preclinical testing. While this class of drugs should technically be referred to as cationic lipophilic, the term cationic amphiphilic is widely used and recognized in this field, and for this reason, the terminology cationic amphiphilic drugs (CADs) will be employed in this Minireview. The aim of this Minireview is to provide an evaluation of the state of knowledge on the functional consequences of CAD-induced phospholipidosis.

Key Words: phospholipidosis • cationic amphiphilic drugs • alveolar macrophages • phagocytosis • amiodarone • lysosomes • rats • mice • phospholipase




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