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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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Bestelakorik adierazi ezean, itemaren baimena horrela deskribatzen da: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/).