Assessment of antifungal drugs’ activity against some Candida albicans isolates in the presence or absence of human albumin: a study employing an in vitro pharmacokinetics / pharmacodynamics model

Abstract

Invasive candidiasis associated with the dissemination of endogenous Candida species is a fatal condition linked to high rates of morbidity and mortality. Progressive drug resistance necessitates the need for prompt and effective therapy. Therefore, choosing a specific and effective treatment is crucial. A two-compartment in vitro pharmacokinetics (PK) / pharmacodynamics (PD) model has been used for this purpose, and the PD behaviours of amphotericin B (AMB; at 2.5 and 5 mg/L), voriconazole (VOR; at 1.5 and 3 mg/L), and itraconazole (ITR; at 1.5 and 3 mg/L) were assessed against two Candida albicans isolates (a sensitive and resistant one; ATCC-90028 and ATCC-10231, re¬spectively) with or without the addition of human albumin (2%). PK were simulated as time-concentration profiles, while the PD susceptibility of all drug doses has been assessed through the minimum inhibitory concentration (MIC), the relative optical density of fungal growth, and the exposure - effect relationship (fAUC0–24/MIC). A fungicidal activity without the presence of albumin was seen against both isolates of C. albicans at the highest dose of VOR, while the addition of albumin potentiated the efficacies of AMB and of VOR against both isolates, with no effect for ITR. Finally, human albumin exerted a variable and dose-dependent effect on the activities of some antifungal agents.