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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9147809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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