| Indication |
Used to treat potentially life threatening fungal infections. |
| Pharmacodynamics |
Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses. |
| Mechanism of action |
Amphotericin B is fungistatic or fungicidal depending on the
concentration obtained in body fluids and the susceptibility of the
fungus. The drug acts by binding to sterols (ergosterol) in the cell
membrane of susceptible fungi. This creates a transmembrane channel, and
the resultant change in membrane permeability allowing leakage of
intracellular components. Ergosterol, the principal sterol in the fungal
cytoplasmic membrane, is the target site of action of amphotericin B
and the azoles. Amphotericin B, a polyene, binds irreversibly to
ergosterol, resulting in disruption of membrane integrity and ultimately
cell death. |
| Absorption |
Bioavailability is 100% for intravenous infusion. |
| Volume of distribution |
Not Available |
| Protein binding |
Highly bound (>90%) to plasma proteins. |
| Metabolism |
Exclusively renal |
| Route of elimination |
Not Available |
| Half life |
An elimination half-life of approximately 15 days follows an initial plasma half-life of about 24 hours. |
| Clearance |
- 39 +/- 22 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 1 mg/kg/day at Day 1]
- 17 +/- 6 mL/hr/kg [febrile neutropenic cancer and bone marrow
transplant patients receiving infusion of 1 mg/kg/day 3-20 days later]
- 51 +/- 44 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 2.5 mg/kg/day at Day 1]
- 22 +/- 15 mL/hr/kg [febrile neutropenic cancer and bone marrow
transplant patients receiving infusion of 2.5 mg/kg/day 3-20 days later]
- 21 +/- 14 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 5 mg/kg/day at Day 1]
- 11 +/- 6 mL/hr/kg [febrile neutropenic cancer and bone marrow
transplant patients receiving infusion of 5 mg/kg/day 3-20 days later]
|
| Toxicity |
Oral, rat: LD50 = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest. |
