ACCUMULATION, RELEASE AND SUBCELLULAR-LOCALIZATION OF AZITHROMYCIN INPHAGOCYTIC AND NON-PHAGOCYTIC CELLS IN CULTURE

The authors have examined the pharmacokinetic parameters of azithromyc in in phagocytic (J774 macrophages) and non-phagocytic (rat embryo fib roblasts and NRK-cells) cultured cells. Azithromycin demonstrates an e xceptionally large accumulation in all the cell types tested (perhaps in two functionally and structurally distinct compartments) and a slow release of the cell-associated drug. Azithromycin probably accumulate s in cells by a non-specific transport process following the model of diffusion/segregation. The cell-associated drug distributes mostly in the lysosomal compartment (50-70%) and the remaining part is freely so luble in the cytosol. In fibroblasts, and to a lesser extent in NRK-ce lls, azithromycin (10 mg/l) induces a decrease of the buoyant density of the lysosomes which may be brought about by the drug itself togethe r with osmotically-bound water and/or by the accumulation of low-densi ty materials within these organelles. These observations open importan t questions with respect to the potential toxicity of azithromycin. Th e significance of such alterations and of their biological consequence s are at present under investigation.