In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>

The aims of this study were to characterize the antifungal activity of amphotericin B against <i>Candida auris</i> 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 s...

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Autores principales:	Unai Caballero, Elena Eraso, Javier Pemán, Guillermo Quindós, Valvanera Vozmediano, Stephan Schmidt, Nerea Jauregizar
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Candida auris</i> PK/PD model amphotericin B time-kill curves Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/e69e23bf110b4853b9214d2e5ab68f2e
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spelling	oai:doaj.org-article:e69e23bf110b4853b9214d2e5ab68f2e2021-11-25T18:40:31ZIn Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>10.3390/pharmaceutics131117671999-4923https://doaj.org/article/e69e23bf110b4853b9214d2e5ab68f2e2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1767https://doaj.org/toc/1999-4923The aims of this study were to characterize the antifungal activity of amphotericin B against <i>Candida auris</i> 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<sub>max</sub> 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 <i>C. auris</i>. 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 <i>C. auris</i> infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for <i>C. auris</i> invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.Unai CaballeroElena ErasoJavier PemánGuillermo QuindósValvanera VozmedianoStephan SchmidtNerea JauregizarMDPI AGarticle<i>Candida auris</i>PK/PD modelamphotericin Btime-kill curvesPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1767, p 1767 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Candida auris</i> PK/PD model amphotericin B time-kill curves Pharmacy and materia medica RS1-441
spellingShingle	<i>Candida auris</i> PK/PD model amphotericin B time-kill curves Pharmacy and materia medica RS1-441 Unai Caballero Elena Eraso Javier Pemán Guillermo Quindós Valvanera Vozmediano Stephan Schmidt Nerea Jauregizar In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>
description	The aims of this study were to characterize the antifungal activity of amphotericin B against <i>Candida auris</i> 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<sub>max</sub> 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 <i>C. auris</i>. 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 <i>C. auris</i> infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for <i>C. auris</i> invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.
format	article
author	Unai Caballero Elena Eraso Javier Pemán Guillermo Quindós Valvanera Vozmediano Stephan Schmidt Nerea Jauregizar
author_facet	Unai Caballero Elena Eraso Javier Pemán Guillermo Quindós Valvanera Vozmediano Stephan Schmidt Nerea Jauregizar
author_sort	Unai Caballero
title	In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>
title_short	In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>
title_full	In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>
title_fullStr	In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>
title_full_unstemmed	In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>
title_sort	in vitro pharmacokinetic/pharmacodynamic modelling and simulation of amphotericin b against <i>candida auris</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e69e23bf110b4853b9214d2e5ab68f2e
work_keys_str_mv	AT unaicaballero invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi AT elenaeraso invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi AT javierpeman invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi AT guillermoquindos invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi AT valvaneravozmediano invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi AT stephanschmidt invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi AT nereajauregizar invitropharmacokineticpharmacodynamicmodellingandsimulationofamphotericinbagainsticandidaaurisi
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In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against <i>Candida auris</i>

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