In vitro PK/PD modeling of bisaryloxypropanamine derivative against Candida spp

Introduction: Systemic fungal infections death is increasing alarmingly and multidrug resistance is one of the main causes¹,²,³. Objective: Evaluate the efficacy of a novel antifungal synthetic molecule (1,3-bis(3,4-dichlorophenoxy)propan-2-aminium chloride) against Candida spp and built a PK/PD model. Methods: A time-kill assay was carried out with the yeasts C. albicans and C. tropicalis. Compound was tested over a range of concentrations: 0 to 8 times the MIC during 48 h. Modified Emax models were used in the modeling. Results: The MIC was 1.56 µg/mL for both yasts investigated. The generation rate constat (k), the EC50 and the kmax were 0.14 ± 0.00 h-1, 4.71 ± 0.38 μg/mL and 2.48 ± 0.51 h-1 for C. albicans; and 0.16 ± 0.00 h-1, 3.13 ± 0.75 μg/mL and 1.89 ± 1.83 h-1 for C. tropicalis. Conclusion: The results support the potential of this molecule as an antifungal candidate.