Caspofungin

Chemical Identity

Property	Value
Chemical Formula	C52H88N10O15
Molecular Weight	1093.31 g/mol
CAS Number	162808-62-0
IUPAC Name	1-[(4R,5S)-5-[(2-aminoethyl)amino]-N2-(10,12-dimethyltetradecanoyl)-4-hydroxy-L-ornithine]-4-[(4S)-4-hydroxy-4-[4-hydroxy-3-(3-hydroxy-L-ornithine)-phenyl]-L-threonine]-5-L-threonine-caspofungin
Peptide Class	Echinocandin Antifungal
Origin	Semi-synthetic from Glarea lozoyensis

Structure

Caspofungin is a semi-synthetic lipopeptide derived from pneumocandin B0, a fermentation product of the fungus Glarea lozoyensis. The hexapeptide core contains several unusual amino acids including dihydroxyhomotyrosine and threonine derivatives. A N-linked fatty acid side chain (10,12-dimethylmyristic acid) contributes to membrane anchoring. An aminoethyl group replaces the hydroxyl group at one position to improve water solubility.

Mechanism of Action

Caspofungin non-competitively inhibits beta-1,3-glucan synthase (FKS1/FKS2 complex), the enzyme responsible for synthesizing beta-1,3-glucan polymers in the fungal cell wall. Beta-1,3-glucan provides structural rigidity to the fungal cell wall; its depletion leads to osmotic instability and cell lysis. The target is absent in mammalian cells, conferring selective toxicity.

Clinical Applications

Caspofungin (Cancidas) is approved for:

• Invasive candidiasis: Including candidemia and deep-seated Candida infections
• Invasive aspergillosis: In patients refractory to or intolerant of amphotericin B
• Esophageal candidiasis: Moderate to severe disease
• Empiric therapy: Febrile neutropenia with suspected fungal infection

Caspofungin is fungicidal against Candida and fungistatic against Aspergillus species.

Pharmacokinetics

• Half-life: 9-11 hours (terminal); 40-50 hours (distribution)
• Protein binding: >96% (primarily albumin)
• Metabolism: Spontaneous chemical degradation; not CYP-mediated
• Elimination: Hepatic metabolism and biliary excretion (41% feces)
• No renal dose adjustment required

Safety and Side Effects

Generally well-tolerated. Common adverse effects include fever (3%), phlebitis at infusion site (3%), headache (3%), and nausea (2%). Hepatotoxicity (elevated liver enzymes) occurs in 2-5% of patients. Histamine-mediated reactions (flushing, rash) with rapid infusion. No significant drug interactions via CYP enzymes, though cyclosporine levels may increase.

References

• Mora-Duarte, J., et al. (2002). Comparison of caspofungin and amphotericin B for invasive candidiasis. New England Journal of Medicine, 347, 2020-2029.
• Maertens, J., et al. (2004). Efficacy and safety of caspofungin for treatment of invasive aspergillosis. Clinical Infectious Diseases, 38, 1540-1547.