Anidulafungin
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N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2R)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.09,13]heptacosan-18-yl]- 4-{4-[4-(pentyloxy)phenyl]phenyl}benzamide
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| Clinical data | |
| Trade names | Eraxis |
| AHFS/Drugs.com | monograph |
| Pharmacokinetic data | |
| Protein binding | 84 % |
| Biological half-life | 40–50 hours |
| Identifiers | |
| CAS Number | 166663-25-8  |
| ATC code | J02AX06 (WHO) |
| PubChem | CID: 166548 |
| DrugBank | DB00362 |
| ChemSpider | 21106258 |
| UNII | 9HLM53094I |
| KEGG | D03211  |
| ChEBI | CHEBI:55346 |
| ChEMBL | CHEMBL1630215 |
| Chemical data | |
| Formula | C58H73N7O17 |
| Molecular mass | 1140.24 g/mol |
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Anidulafungin (brand names: Eraxis (in U.S. and Russia), Ecalta (in Europe)) is a semisynthetic echinocandin used as an antifungal drug. Anidulafungin was originally manufactured and submitted for FDA approval by Vicuron Pharmaceuticals.[1] Pfizer acquired the drug upon its acquisition of Vicuron in the fall of 2005.[2] Pfizer gained approval by the Food and Drug Administration (FDA) on February 21, 2006;[3] it was previously known as LY303366. Preliminary evidence indicates it has a similar safety profile to caspofungin. Anidulafungin has proven efficacy against esophageal candidiasis, but its main use will probably be in invasive Candida infection;[4][5][6] it may also have application in treating invasive Aspergillus infection. It is a member of the class of antifungal drugs known as the echinocandins; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall.
Pharmacodynamics and pharmacokinetics
Anidulafungin significantly differs from other antifungals in that it undergoes chemical degradation to inactive forms at body pH and temperature. Because it does not rely on enzymatic degradation or hepatic or renal excretion, the drug is safe to use in patients with any degree of hepatic or renal impairment.[7]
Distribution: 30–50 L. Protein binding: 84%.
Anidulafungin is evidently metabolized by the liver. This specific drug undergoes slow chemical hydrolysis to an open-ring peptide which lacks antifungal activity. The half-life of the drug is 27 hours. Thirty percent is excreted in the feces (10% as unchanged drug). Less than 1% is excreted in the urine.[8][9][10]
Mechanism of action
Anidulafungin inhibits glucan synthase, an enzyme important in the formation of (1→3)-β-D-glucan, a major fungal cell wall component. Glucan synthase is not present in mammalian cells, so it is an attractive target for antifungal activity.[11]
Semisynthesis
Anidulafungin is manufactured via semisynthesis. The starting material is echinocandin B (a lipopeptide fermentation product of Aspergillus nidulans or the closely related species, A. rugulosus), which undergoes deacylation (cleavage of the linoleoyl side chain) by the action of a deacylase enzyme from the bacterium Actinoplanes utahensis;[12] in three subsequent synthetic steps, including a chemical reacylation, the antifungal drug anidulafungin[13][11] is synthesized.
References
- ↑ PRNewswire. Vicuron Pharmaceuticals Files New Drug Application (NDA) for Anidulafungin for Treatment of Invasive Candidiasis/Candidemia 08-18-2005.
- ↑ PRNewswire. Vicuron Pharmaceuticals Stockholders Approve Merger With Pfizer 08-15-2005
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- ↑ Trissel LA and Ogundele AB, "Compatibility of Anidulafungin With Other Drugs During Simulated Y-Site Administration,"Am J Health-Sys Pharm, 2005, 62:834-7.
- ↑ Vazquez JA, "Anidulafungin: A New Echinocandin With a Novel Profile," Clin Ther, 2005, 27(6):657-73.
- ↑ Walsh TJ, Anaissie EJ, Denning DW, et al, "Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America," Clin Infect Dis, 2008, 46(3):327-60
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