Mb. Carlier et al., ACCUMULATION, RELEASE AND SUBCELLULAR-LOCALIZATION OF AZITHROMYCIN INPHAGOCYTIC AND NON-PHAGOCYTIC CELLS IN CULTURE, International journal on tissue reactions, 16(5-6), 1994, pp. 211-220
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.