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Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes

W L Hand1, D L Hand

  • 1Departments of Research Development and Internal Medicine, Texas Tech. University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX 79905, USA. medewlh@ttuhsc.edu

International Journal of Antimicrobial Agents
|November 17, 2001
PubMed

Insights

Azithromycin is highly concentrated and retained by human immune cells (polymorphonuclear leukocytes), suggesting it can effectively target infections at tissue sites.

Area of Science:

  • Pharmacology
  • Immunology
  • Microbiology

Background:

  • Azithromycin exhibits prolonged tissue concentrations despite low serum levels.
  • Its efficacy suggests activity at infection sites within tissues.
  • Understanding its interaction with immune cells is crucial.

Purpose of the Study:

  • To evaluate the interaction between azithromycin and human polymorphonuclear leukocytes (PMN).
  • To determine the uptake, retention, and release kinetics of azithromycin by PMN.

Main Methods:

  • Utilized radiolabeled azithromycin to quantify cellular accumulation in PMN.
  • Employed velocity-gradient centrifugation to determine drug concentration ratios (C/E).
  • Investigated the influence of metabolic inhibitors and phagocytosis on azithromycin uptake.

Main Results:

  • Azithromycin was significantly accumulated by human PMN, with a C/E ratio of 387.2 at 2 hours.
  • Uptake was independent of cellular metabolism inhibitors but slightly reduced by phagocytosis.
  • Azithromycin demonstrated extremely slow release (efflux) from PMN.
  • Agents neutralizing lysosomal pH increased azithromycin efflux.

Conclusions:

  • Human PMN actively accumulate and retain azithromycin.
  • This cellular accumulation and prolonged retention facilitate drug delivery to infection sites.
  • Azithromycin's interaction with phagocytic cells supports its therapeutic effectiveness in tissues.

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