PK/PD modeling of 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride antifungal activity against Microsporum canis and Trichophyton mentagrophytes

Introduction: The incidence of fungal infections is increasing. Therefore, the development of new treatment options is necessary1. Objective: To evaluate the fungicidal activity of the synthetic compound 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride through time-kill studies and pharmacokinetic/pharmacodynamic (PK/PD) modeling. Methods: Time-kill curves were built with Microsporum canis and Trichophyton mentagrophytes using concentrations multiples of the compound’s MIC. The curves were fit using an Emax-model2,3,4 and the PK/PD parameters determined. Results: The generation rate constant (k), EC50 and kmax were 0.10 ± 0.00 h-1, 3.59 ± 0.26 μg/mL and 2.84 ± 2.61 h-1 for M. canis; and 0.15 ± 0.00 h-1, 4.69 ± 0.24 μg/mL and 2.37 ± 2.16 h-1 for T. mentagrophytes, respectively. The fungicidal concentrations were 6.24 μg/mL for M. canis and 12.48 μg/mL for T. mentagrophytes, 0.24 h and 0.29 h after exposure. Conclusion: The maximum fungicidal effect is achieved in less than 1 h post-exposure, indicating an extremely rapid effect.