[Mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes].
Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be effective at tissue sites of infection. These unique features prompted us to evaluate the interactions of azithromycin and human polymorphonuclear leukocytes (PMN). Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E). Azithromycin was massively accumulated by human PMN (C/E = 387.2 at 2 h). Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN. After removal of extracellular drug, the release (efflux) of azithromycin from PMN was extremely slow. Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux. Active concentration and prolonged retention of azithromycin by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.
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Department of Research Development and Internal Medicine, Texas Tech. University Health Sciences Center, Texas, USA.
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D000241:Adenosine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D017963:Azithromycin / Q000097:blood*; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D017680:Potassium Compounds / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D013696:Temperature
D000596:Amino Acids; D004791:Enzyme Inhibitors; D017680:Potassium Compounds; D017963:Azithromycin; C033320:potassium fluoride; D019810:Sodium Azide; D000241:Adenosine; D012966:Sodium Cyanide; D005459:Fluorides