In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B Against

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2021 Nov 27

PMID 34834182

Citations 5

Authors

Unai Caballero

Elena Eraso

Javier Peman

Guillermo Quindos

Valvanera Vozmediano

Stephan Schmidt

Nerea Jauregizar

Affiliations

Soon will be listed here.

Abstract

The aims of this study were to characterize the antifungal activity of amphotericin B against in a static in vitro system and to evaluate different dosing schedules and MIC scenarios by means of semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modelling and simulation. A two-compartment model consisting of a drug-susceptible and a drug-resistant subpopulation successfully characterized the time-kill data and a modified E sigmoidal model best described the effect of the drug. The model incorporated growth rate constants for both subpopulations, a death rate constant and a transfer constant between both compartments. Additionally, the model included a parameter to account for the delay in growth in the absence or presence of the drug. Amphotericin B displayed a concentration-dependent fungicidal activity. The developed PK/PD model was able to characterize properly the antifungal activity of amphotericin B against . Finally, simulation analysis revealed that none of the simulated standard dosing scenarios of 0.6, 1 and 1.5 mg/kg/day over a week treatment showed successful activity against infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.

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