In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against Candida auris
dc.contributor.author | Caballero Cuenca, Unai | |
dc.contributor.author | Eraso Barrio, María Elena | |
dc.contributor.author | Pemán, Javier | |
dc.contributor.author | Quindós Andrés, Guillermo | |
dc.contributor.author | Vozmediano, Valvanera | |
dc.contributor.author | Schmidt, Stephan | |
dc.contributor.author | Jauregizar Albonigamayor, Nerea | |
dc.date.accessioned | 2021-12-01T09:08:35Z | |
dc.date.available | 2021-12-01T09:08:35Z | |
dc.date.issued | 2021-10-22 | |
dc.identifier.citation | Pharmaceutics 13(11) : (2021) // Article ID 1767 | es_ES |
dc.identifier.issn | 1999-4923 | |
dc.identifier.uri | http://hdl.handle.net/10810/54243 | |
dc.description.abstract | The aims of this study were to characterize the antifungal activity of amphotericin B against Candida auris 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 Emax 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 C. auris. 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 C. auris infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for C. auris invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported. | es_ES |
dc.description.sponsorship | This research was funded by Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza, GIC15/78 IT-990-16 and by FIS, Spain, PI17/01538. U.C. was funded by a Ph.D. grant from the University of the Basque Country, PIF 17/266. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | candida auris | es_ES |
dc.subject | PK/PD model | es_ES |
dc.subject | amphotericin B | es_ES |
dc.subject | time-kill curves | es_ES |
dc.title | In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against Candida auris | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2021-11-25T16:00:09Z | |
dc.rights.holder | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1999-4923/13/11/1767/htm | es_ES |
dc.identifier.doi | 10.3390/pharmaceutics13111767 | |
dc.departamentoes | Farmacología | |
dc.departamentoes | Inmunología, microbiología y parasitología | |
dc.departamentoeu | Farmakologia | |
dc.departamentoeu | Immunologia, mikrobiologia eta parasitologia |
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Except where otherwise noted, this item's license is described as 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).