Amphotericin B deoxycholate causes significant nephrotoxicity. Lipid formulations of amphotericin B (liposomal amphotericin B — L-AmB) reduce nephrotoxicity by which mechanism?

• A Liposomes increase amphotericin B plasma protein binding, reducing free drug available for renal clearance
• B Liposomal formulation converts amphotericin B to a pro-drug that requires esterase activation in fungal cells only
• C Liposomal encapsulation prevents amphotericin B from reaching renal tubular cells; drug is preferentially delivered to fungal cell membranes via lipid transfer to ergosterol-rich membranes ✓
• D Liposomes bypass renal proximal tubular uptake by the megalin endocytic pathway, reducing tubular cell drug concentration

Explanation

The mechanism underlying reduced nephrotoxicity of lipid AmB formulations is preferential delivery and ergosterol targeting: amphotericin B has much higher affinity for ergosterol (fungal membranes) than cholesterol (mammalian membranes), with a ~10:1 binding selectivity. Liposomal encapsulation acts as a delivery vehicle — the intact liposome is inert to renal tubular cells but preferentially transfers its drug payload to ergosterol-rich fungal cell membranes via lipid exchange/fusion, reducing free drug concentrations reaching renal proximal tubular cells (which contain cholesterol). Additionally, liposomes are taken up by the mononuclear phagocyte system, delivering drug to macrophages harboring intracellular fungi. Tubular megalin plays a role in conventional AmB but not the primary L-AmB mechanism.

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

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Written and medically reviewed by the StethoPrep medical team.