Cellular uptake and subcellular distribution of roxithromycin and erythromycin in phagocytic cells

The intracellular accumulation and subcellular distribution of 14C-labelled roxithromycin and erythromycin has been studied in macrophages and polymorphonuclear neutrophils of both human and animal origin. Roxithromycin was consistently and significantly more accumulated than erythromycin, reaching intracellular/extracellular concentration ratios between 14 (in polymorphonuclear neutrophils) and 190 (in alveolar macrophages from smokers). Uptake was reversible, insensitive to anaerobiosis and to the presence of an aminoglycoside, but inhibited by acid pH. Upon subcellular fractionation by isopycnic centrifugation in sucrose gradients., half the roxithromycin or erythromycin recovered in cell homogenates was found associated with the lysosomes in macrophages, and about one third with azurophil granules in polymorphonuclear leucocytes. Inasmuch as cellular uptake is a necessary, albeit not sufficient, condition for antimicrobials to kill or inhibit the growth of intracellular bacteria the properties of roxithromycin may give it a distinct advantage over other antimicrobial agents.