Amphotericin B
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| (1R-(1R*,3S*,5R*,6R*,9R*,11R*,15S*,16R*,17R*, 18S*,19E,21E,23E,25E,27E,29E,31E,33R*, 35S*,36R*,37S*))-33-((3-Amino-3,6-dideoxy-beta- D-mannopyranosyl)oxy)- 1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl -13-oxo-14,39-dioxabicyclo(33.3.1)nonatriaconta- 19,21,23,25,27,29,31-heptaene-36- carboxylic acid | |
| CAS number 1397-89-3 | ATC code A01AB04, A07AA07, G01AA03, J02AA01 |
| Chemical formula | C47H75NO17 |
| Molecular weight | 924.084 |
| Bioavailability | ? |
| Metabolism | ? |
| Elimination half-life | ? |
| Excretion | ? |
| Pregnancy category | ? |
| Legal status | ? |
| Routes of administration | ? |
Amphotericin B (Fungilin®, Fungizone®, Abelcet®, AmBisome®, Amphocil®) is a polyene antimycotic drug, used intravenously in systemic fungal infections. It was originally extracted from Streptomyces nodosus fungi.
AmBisome is a liposomal formulation of amphotericin B for injection, developed by NeXstar Pharmaceuticals (acquired by Gilead Sciences in 1999). It is marketed by Gilead in Europe and licensed to Fujisawa Healthcare for marketing in the USA, and Sumitomo Pharmaceuticals in Japan.
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Uses
Oral preparations of amphotericin B are rarely used. The main use is in systemic fungal infections (e.g. in immunocompromised patients), and in visceral leishmaniasis. Aspergillosis, cryptococcus infections (e.g. meningitis) and candidiasis are treated with amphotericin B. It is also used empirically in febrile immunocompromised patients who do not respond to broad-spectrum antibiotics.
Method of action
As with other polyene antifungals, amphotericin B associates with ergosterol, a membrane chemical of fungi, forming a pore that leads to K+ leakage and fungal cell death. Recently, however, researchers found evidence that pore formation is not necessarily linked to cell death (i.e. Angewandte Chemie Int. Ed. Engl. 2004). The actual mechanism of action may be more complex and multi-faceted.
Side effects
Side-effects can be severe; nephrotoxicity (kidney damage) is a major issue. Other side-effects include headache, vomiting, convulsions and fever; it has to be withdrawn occasionally from patients to determine whether their fever is due to amphotericin B or an actual infection. A similar problem exists with cytarabine.
The side-effects are much milder when amphotericin B is delivered in liposomes (AmBisome). This preparation is more expensive, but makes the drug more tolerable, especially in patients with known renal failure.
External link
- AmBisome web site (http://www.ambisome.com) run by Fujisawa Healthcare
- Chembank entry (http://chembank.med.harvard.edu/compounds/display.html?compound_id=2960&)de:Amphotericin B