Azithromycin achieves tissue concentrations 10–100 times higher than plasma concentrations. The pharmacokinetic property responsible for this is:
- A High plasma protein binding retaining the drug in the vascular compartment
- B Rapid hepatic first-pass metabolism producing active metabolites that concentrate in tissues
- C Very large volume of distribution due to extensive intracellular sequestration in lysosomes and phagocytes ✓
- D Renal tubular secretion directing the drug to the renal medulla
Correct answer: C. Very large volume of distribution due to extensive intracellular sequestration in lysosomes and phagocytes
Explanation
Azithromycin has a volume of distribution exceeding 30 L/kg (compared to ~0.3 L/kg for amoxicillin), reflecting massive sequestration in tissue phagocytes (macrophages, neutrophils, fibroblasts). Being a weak base, it becomes ion-trapped in acidic intracellular compartments (lysosomes, phagolysosomes), reaching concentrations far exceeding plasma. This is pharmacologically advantageous for intracellular pathogens (Legionella, Chlamydia, Mycoplasma) and explains the prolonged tissue half-life (~68 hours) allowing once-daily and short-course regimens.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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