PK/PD modeling and simulation of the in vitro activity of the combinations of isavuconazole with echinocandins against Candida auris
dc.contributor.author | Caballero Cuenca, Unai | |
dc.contributor.author | Eraso Barrio, María Elena ![]() | |
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 | 2024-04-29T17:59:36Z | |
dc.date.available | 2024-04-29T17:59:36Z | |
dc.date.issued | 2023-06 | |
dc.identifier.citation | CPT: Pharmacometrics & Systems Pharmacology 12(6) : 770-782 (2023) | es_ES |
dc.identifier.issn | 2163-8306 | |
dc.identifier.issn | 2163-8306 | |
dc.identifier.uri | http://hdl.handle.net/10810/66932 | |
dc.description.abstract | In vitro combination of echinocandins and isavuconazole against the emerging species Candida auris is mainly synergistic. However, this combination has not been evaluated in clinical settings. A pharmacokinetic/pharmacodynamic modeling and simulation approach based on in vitro data may be helpful to further study the therapeutic potential of these combinations. Therefore, the aims of this study were to characterize the time course of growth and killing of C. auris in response to the combination of the three approved echinocandins and isavuconazole using a semimechanistic model and to perform model-based simulations in order to predict the in vivo response to combination therapy. In vitro static time-kill curve data for isavuconazole and echinocandins combinations against six blood isolates of C. auris were best modeled considering the total killing of the fungal population as dependent on the additive effects of both drugs. Once assessed, the predictive performance of the model using simulations of different dosing and fungal susceptibility scenarios were conducted. Model-based simulations revealed that none of the combinations at standard or higher dosages would be effective against the studied isolates of C. auris and it was predicted that the combinations of isavuconazole with anidulafungin or caspofungin would be effective for minimum inhibitory concentrations up to 0.03 and 0.06 mg/L respectively, whereas the combination with micafungin would lead to treatment failure. The current approach highlights the importance of bridging the in vitro results to the clinic. | 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, FIS PI17/01538, and MCINN PID2020-117983RB-I00. U.C. was funded by a PhD grant from the University of the Basque Country, PIF 17/266. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2020-117983RB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es/ | * |
dc.title | PK/PD modeling and simulation of the in vitro activity of the combinations of isavuconazole with echinocandins against Candida auris | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | es_ES |
dc.rights.holder | Atribución-NoComercial 3.0 España | * |
dc.relation.publisherversion | https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.12949 | es_ES |
dc.identifier.doi | 10.1002/psp4.12949 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoes | Inmunología, microbiología y parasitología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
dc.departamentoeu | Immunologia, mikrobiologia eta parasitologia | es_ES |
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Except where otherwise noted, this item's license is described as © 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.