Accumulation, Release and Subcellular-localization of Azithromycin in Phagocytic and Non-phagocytic Cells in Culture

The authors have examined the pharmacokinetic parameters of azithromycin in phagocytic (J774 macrophages) and non-phagocytic (rat embryo fibroblasts and NRK-cells) cultured cells. Azithromycin demonstrates an exceptionally 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 accumulates 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 soluble in the cytosol. In fibroblasts, and to a lesser extent in NRK-cells, azithromycin (10 mg/l) induces a decrease of the buoyant density of the lysosomes which may be brought about by the drug itself together with osmotically-bound water and/or by the accumulation of low-density materials within these organelles. These observations open important questions with respect to the potential toxicity of azithromycin. The significance of such alterations and of their biological consequences are at present under investigation