Azithromycin achieves very high tissue concentrations (100–1000 times plasma levels) in macrophages and polymorphonuclear cells. What property accounts for this?

• A Azithromycin is actively transported into cells by organic anion transporting polypeptide (OATP1B1)
• B Azithromycin binds intracellular actin, preventing its redistribution to plasma
• C Azithromycin is a basic amine that is ion-trapped in acidic intracellular compartments (lysosomes, phagolysosomes) ✓
• D Azithromycin has very high plasma protein binding, preventing renal clearance

Explanation

Azithromycin is a weakly basic molecule (pKa ~8.7) that passively diffuses into cells in its uncharged form. Once inside the acidic milieu of phagolysosomes (pH ~4.5–5), it becomes protonated (ionised), cannot diffuse back out (ion trapping), and accumulates in concentrations 100–1000 times higher than plasma. This lysosomal trapping makes azithromycin ideal for treating intracellular pathogens such as Chlamydia, Legionella, and Mycobacteria.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.