Drug intelligence / Profile preview

caspofungin + liposomal amphotericin B + voriconazole

Development stage
Preclinical
Lead developer
Merck
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a combination antifungal therapy consisting of three agents with distinct mechanisms of action: - **Caspofungin** is an echinocandin that inhibits the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall. - **Liposomal amphotericin B** is a polyene antifungal that binds to ergosterol in fungal cell membranes, creating pores and causing cell death. The liposomal formulation reduces nephrotoxicity compared to conventional amphotericin B. - **Voriconazole** is a triazole antifungal that inhibits fungal cytochrome P450-dependent 14α-lanosterol demethylation, disrupting ergosterol synthesis and compromising membrane integrity. This triple combination has been used as salvage or rescue therapy for severe invasive fungal infections (IFIs), particularly in immunocompromised patients or those with refractory disease such as invasive aspergillosis. The rationale for combining these drugs lies in their complementary mechanisms and potential synergistic effects against resistant or difficult-to-treat fungi[1][5][6]. Clinical experience suggests this regimen can be effective when monotherapy fails, though robust prospective data are limited.

02

Targets

CYP51A1 (Sterol 14α-demethylase)ErgosterolFKS (1,3-beta-D-glucan synthase component FKS1)

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