Caspofungin

Chemical Identity

Property	Value
Chemical Formula	C52H88N10O15
Molecular Weight	1093.31 Da
CAS Number	179463-17-3
Peptide Class	Lipopeptide (Echinocandin)
Origin	Semi-synthetic (from Glarea lozoyensis)

Structure

Caspofungin is a semi-synthetic lipopeptide derived from pneumocandin B0, a fermentation product of Glarea lozoyensis. The molecule contains a cyclic hexapeptide core with three hydroxyornithine residues and an N-linked fatty acyl side chain (linoleoyl group). The hemiaminal at position 5 is replaced with an ethylenediamine group.

Mechanism of Action

Caspofungin non-competitively inhibits beta-1,3-D-glucan synthase, an enzyme essential for fungal cell wall biosynthesis. This enzyme is absent in mammalian cells, providing selectivity. Inhibition of glucan synthesis leads to cell wall weakening, osmotic instability, and fungal cell death. It is fungicidal against Candida and fungistatic against Aspergillus.

Clinical Applications

• Invasive candidiasis: First-line therapy for candidemia
• Invasive aspergillosis: Salvage therapy after azole failure
• Esophageal candidiasis: Second-line after fluconazole
• Empiric antifungal therapy: Febrile neutropenia

Pharmacokinetics

• Half-life: 9-11 hours (terminal 40-50 hours)
• Protein binding: 96%
• Metabolism: Hydrolysis and N-acetylation
• Elimination: Hepatic (41% fecal, 14% renal)
• Loading dose: 70 mg day 1, then 50 mg daily

Safety and Side Effects

Hepatotoxicity (elevated ALT/AST), histamine-related reactions (rash, facial swelling, pruritus with rapid infusion), hypokalemia, and fever. Generally well-tolerated compared to amphotericin B.

References

• Mora-Duarte, J., et al. (2002). Caspofungin versus amphotericin B for invasive candidiasis. New England Journal of Medicine, 347, 2020-2029.
• Denning, D.W. (2003). Echinocandin antifungal drugs. Lancet, 362, 1142-1151.