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[Mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes]

W I Hand1, D L Hand

  • 1Department of Research Development and Internal Medicine, Texas Tech. University Health Sciences Center, Texas, USA.

Antibiotiki I Khimioterapiia = Antibiotics and Chemoterapy [Sic]
|January 9, 2003
PubMed

Insights

Azithromycin accumulates significantly in human white blood cells (polymorphonuclear leukocytes), retaining it for extended periods. This cellular accumulation suggests a mechanism for targeted drug delivery to infection sites.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Immunology

Context:

  • Azithromycin exhibits high tissue concentrations and low serum levels, indicating unique pharmacokinetic properties.
  • Understanding azithromycin's interaction with immune cells is crucial for explaining its efficacy at infection sites.

Purpose:

  • To investigate the uptake, retention, and release mechanisms of azithromycin by human polymorphonuclear leukocytes (PMN).

Summary:

  • Azithromycin is extensively accumulated by human PMN, with a cellular to extracellular concentration ratio (C/E) of 387.2 at 2 hours.
  • Uptake was independent of cellular metabolism inhibitors but slightly reduced by phagocytosis.
  • Azithromycin efflux from PMN was very slow, but significantly increased when lysosomal pH was neutralized, suggesting pH-dependent trapping.

Impact:

  • The prolonged retention of azithromycin within phagocytic cells facilitates drug delivery and release at infection foci.
  • This cellular accumulation mechanism enhances azithromycin's therapeutic effectiveness in treating infections.

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