Drug intelligence / Profile preview

amphotericin B + flucytosine + fluconazole

Development stage
Preclinical
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a triple antifungal combination therapy consisting of amphotericin B, flucytosine, and fluconazole. The combination has been studied primarily for the treatment of cryptococcal meningitis, particularly in HIV-infected patients. Research indicates that this triple combination may provide enhanced antifungal activity compared to dual combinations or monotherapy. In murine models of cryptococcal meningitis, the triple combination of amphotericin B colloidal dispersion (ABCD) plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity[2]. The combination works through multiple mechanisms: amphotericin B disrupts fungal cell membranes, flucytosine interferes with fungal protein synthesis, and fluconazole inhibits ergosterol synthesis in fungal cell membranes. Clinical studies have shown that the triple combination may lead to more rapid cerebrospinal fluid (CSF) sterilization and potentially improved mortality outcomes compared to standard therapies in cryptococcal meningitis[8].

02

Targets

CYP51A1 (Sterol 14α-demethylase)ErgosterolTS (Thymidylate synthase)

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