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Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants

Vitamin D (VD) seems to influence drug clearance and outcome. Antifungal drugs (AFU) are the most used azoles in clinical practice. In the literature, no data are available concerning VD’s impact on AFU therapy. The aim of this study was to analyze if VD pathway-related polymorphisms may influence v...

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Autores principales: Cusato, Jessica, Palermiti, Alice, Manca, Alessandra, Mula, Jacopo, Antonucci, Miriam, De Nicolò, Amedeo, Allegra, Sarah, De Francia, Silvia, Chiara, Francesco, Di Perri, Giovanni, Rosa, Francesco Giuseppe De, Calcagno, Andrea, D’Avolio, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147809/
https://www.ncbi.nlm.nih.gov/pubmed/35631455
http://dx.doi.org/10.3390/ph15050630
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author Cusato, Jessica
Palermiti, Alice
Manca, Alessandra
Mula, Jacopo
Antonucci, Miriam
De Nicolò, Amedeo
Allegra, Sarah
De Francia, Silvia
Chiara, Francesco
Di Perri, Giovanni
Rosa, Francesco Giuseppe De
Calcagno, Andrea
D’Avolio, Antonio
author_facet Cusato, Jessica
Palermiti, Alice
Manca, Alessandra
Mula, Jacopo
Antonucci, Miriam
De Nicolò, Amedeo
Allegra, Sarah
De Francia, Silvia
Chiara, Francesco
Di Perri, Giovanni
Rosa, Francesco Giuseppe De
Calcagno, Andrea
D’Avolio, Antonio
author_sort Cusato, Jessica
collection PubMed
description Vitamin D (VD) seems to influence drug clearance and outcome. Antifungal drugs (AFU) are the most used azoles in clinical practice. In the literature, no data are available concerning VD’s impact on AFU therapy. The aim of this study was to analyze if VD pathway-related polymorphisms may influence voriconazole (VRC), itraconazole (ITC), and posaconazole (PSC) drug concentrations in order to identify patients with the highest probability of response and toxicity. Allelic discrimination was performed through real-time PCR, whereas drug concentrations were through liquid chromatography. A total of 636 samples of AFU-treated patients were included in the analysis. Concerning VRC, concentrations higher than the 1000 ng/mL efficacy cut-off value were predicted by Caucasian ethnicity, CYP24A1 3999, and CYP27B1 + 2838 polymorphisms, whereas levels higher than the 5000 ng/mL toxicity value by Caucasian, female sex, e.v. administration, and GC 1296. Considering PSC, concentrations higher than the 700 ng/mL efficacy cut-off value were predicted by VDR Cdx2, CYP27B1 − 1260, and GC 1296. Finally, for ITC, VDR BsmI was the only predictor of drug exposure higher than the 500 ng/mL efficacy cut-off value, whereas female sex, CYP27B1 − 1260, and VDR TaqI remained in the final regression model related to concentrations higher than the 1000 ng/mL toxicity-associated cut-off value. This is the first study reporting the influence of VD pathway-related gene SNPs on AFU exposures, efficacy, and toxicity.
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spelling pubmed-91478092022-05-29 Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants Cusato, Jessica Palermiti, Alice Manca, Alessandra Mula, Jacopo Antonucci, Miriam De Nicolò, Amedeo Allegra, Sarah De Francia, Silvia Chiara, Francesco Di Perri, Giovanni Rosa, Francesco Giuseppe De Calcagno, Andrea D’Avolio, Antonio Pharmaceuticals (Basel) Article Vitamin D (VD) seems to influence drug clearance and outcome. Antifungal drugs (AFU) are the most used azoles in clinical practice. In the literature, no data are available concerning VD’s impact on AFU therapy. The aim of this study was to analyze if VD pathway-related polymorphisms may influence voriconazole (VRC), itraconazole (ITC), and posaconazole (PSC) drug concentrations in order to identify patients with the highest probability of response and toxicity. Allelic discrimination was performed through real-time PCR, whereas drug concentrations were through liquid chromatography. A total of 636 samples of AFU-treated patients were included in the analysis. Concerning VRC, concentrations higher than the 1000 ng/mL efficacy cut-off value were predicted by Caucasian ethnicity, CYP24A1 3999, and CYP27B1 + 2838 polymorphisms, whereas levels higher than the 5000 ng/mL toxicity value by Caucasian, female sex, e.v. administration, and GC 1296. Considering PSC, concentrations higher than the 700 ng/mL efficacy cut-off value were predicted by VDR Cdx2, CYP27B1 − 1260, and GC 1296. Finally, for ITC, VDR BsmI was the only predictor of drug exposure higher than the 500 ng/mL efficacy cut-off value, whereas female sex, CYP27B1 − 1260, and VDR TaqI remained in the final regression model related to concentrations higher than the 1000 ng/mL toxicity-associated cut-off value. This is the first study reporting the influence of VD pathway-related gene SNPs on AFU exposures, efficacy, and toxicity. MDPI 2022-05-20 /pmc/articles/PMC9147809/ /pubmed/35631455 http://dx.doi.org/10.3390/ph15050630 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Cusato, Jessica
Palermiti, Alice
Manca, Alessandra
Mula, Jacopo
Antonucci, Miriam
De Nicolò, Amedeo
Allegra, Sarah
De Francia, Silvia
Chiara, Francesco
Di Perri, Giovanni
Rosa, Francesco Giuseppe De
Calcagno, Andrea
D’Avolio, Antonio
Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants
title Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants
title_full Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants
title_fullStr Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants
title_full_unstemmed Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants
title_short Antifungal Drug Plasma Exposures: A Possible Contribution of Vitamin D-Related Gene Variants
title_sort antifungal drug plasma exposures: a possible contribution of vitamin d-related gene variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147809/
https://www.ncbi.nlm.nih.gov/pubmed/35631455
http://dx.doi.org/10.3390/ph15050630
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