Small molecule
PubChem CID 5280965
Amphotericin B
AmBisome
- Mechanism of action
- Binds fungal ergosterol, forming membrane pores that cause ion leakage
- In plain language
- Punches holes in fungal cell membranes by grabbing onto a molecule unique to fungi, causing the cell's contents to leak out.
- How it works
- Amphotericin B, the active moiety in the liposomal formulation AmBisome, binds to ergosterol, the dominant sterol in the fungal cell membrane. This binding creates transmembrane channels that increase membrane permeability, allowing monovalent ions such as sodium, potassium, hydrogen, and chloride to leak out of the cell, leading to fungal cell death. Amphotericin B has a higher binding affinity for ergosterol than for cholesterol, the analogous sterol in mammalian cell membranes, but it can still bind cholesterol and cause cytotoxicity in human cells, a property that underlies the drug's characteristic toxicity. Encapsulating amphotericin B in a liposome, as in AmBisome, has been shown to allow the drug to penetrate the cell wall of both extracellular and intracellular forms of susceptible fungi. The manufacturer's label also notes that resistant mutants with decreased amphotericin B susceptibility have been isolated after serial passage in drug-containing culture media and from some patients on prolonged therapy.
- Therapeutic applications
- AmBisome is indicated for empirical therapy of presumed fungal infection in febrile, neutropenic patients; for treatment of cryptococcal meningitis in HIV-infected patients; and for treatment of Aspergillus, Candida, and Cryptococcus species infections refractory to amphotericin B deoxycholate, or in patients where renal impairment or unacceptable toxicity precludes use of amphotericin B deoxycholate. It is also indicated for visceral leishmaniasis, though the label notes relapse rates were high in immunocompromised patients following initial parasitologic clearance. The clinical program supporting these indications included eleven studies enrolling 2,171 patients, comparing AmBisome to conventional amphotericin B deoxycholate and, in one trial, to amphotericin B lipid complex (Abelcet).
- Class
- Small molecule
- Therapeutic area
- Antifungal
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