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A retrospective analysis of patient-specific factors on voriconazole clearance

BACKGROUND: Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. We investigated the relationships of voriconazole concentration with patient-specific variables and concomitant medication to identify clinical factors affecting voriconazole c...

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Autores principales: Dote, Satoshi, Sawai, Maki, Nozaki, Ayumu, Naruhashi, Kazumasa, Kobayashi, Yuka, Nakanishi, Hirokazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835838/
https://www.ncbi.nlm.nih.gov/pubmed/27096102
http://dx.doi.org/10.1186/s40780-016-0044-9
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author Dote, Satoshi
Sawai, Maki
Nozaki, Ayumu
Naruhashi, Kazumasa
Kobayashi, Yuka
Nakanishi, Hirokazu
author_facet Dote, Satoshi
Sawai, Maki
Nozaki, Ayumu
Naruhashi, Kazumasa
Kobayashi, Yuka
Nakanishi, Hirokazu
author_sort Dote, Satoshi
collection PubMed
description BACKGROUND: Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. We investigated the relationships of voriconazole concentration with patient-specific variables and concomitant medication to identify clinical factors affecting voriconazole clearance. METHODS: A retrospective chart review of voriconazole trough concentration, laboratory data, and concomitant medication in patients was performed. The concentration/dose ratio (C/D-ratio) was assessed as a surrogate marker of total clearance by dividing voriconazole concentration by daily dose per kg of body weight. RESULTS: A total of 77 samples from 63 patients were obtained. In multiple linear regression analysis, increased C-reactive protein (CRP) level (p < 0.05) and decreased albumin (Alb) level (p < 0.05) were associated with significantly increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was associated with significantly (p < 0.05) decreased C/D-ratio of voriconazole (adjusted r(2) = 0.31). Regarding CRP and Alb, receiver operating characteristic curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole. For CRP, area under the curve (AUC) and cutoff value were 0.71 (95 % confidence interval (CI), 0.57–0.86, p < 0.01) and 4.7 mg/dl, respectively. For Alb, AUC and cutoff value were 0.68 (95 % CI, 0.53–0.82, p < 0.05) and 2.7 g/dl, respectively. A significant difference was seen in voriconazole trough concentration between patients with hepatotoxicity and those without (5.69 μg/ml vs 3.0 μg/ml, p < 0.001). CONCLUSION: Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance. We propose that early measurement of voriconazole concentration before the plateau phase will lead to avoidance of a toxic voriconazole level in patients with elevated CRP level and hypoalbuminemia, although further studies are needed to confirm our findings.
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spelling pubmed-48358382016-04-20 A retrospective analysis of patient-specific factors on voriconazole clearance Dote, Satoshi Sawai, Maki Nozaki, Ayumu Naruhashi, Kazumasa Kobayashi, Yuka Nakanishi, Hirokazu J Pharm Health Care Sci Research Article BACKGROUND: Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. We investigated the relationships of voriconazole concentration with patient-specific variables and concomitant medication to identify clinical factors affecting voriconazole clearance. METHODS: A retrospective chart review of voriconazole trough concentration, laboratory data, and concomitant medication in patients was performed. The concentration/dose ratio (C/D-ratio) was assessed as a surrogate marker of total clearance by dividing voriconazole concentration by daily dose per kg of body weight. RESULTS: A total of 77 samples from 63 patients were obtained. In multiple linear regression analysis, increased C-reactive protein (CRP) level (p < 0.05) and decreased albumin (Alb) level (p < 0.05) were associated with significantly increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was associated with significantly (p < 0.05) decreased C/D-ratio of voriconazole (adjusted r(2) = 0.31). Regarding CRP and Alb, receiver operating characteristic curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole. For CRP, area under the curve (AUC) and cutoff value were 0.71 (95 % confidence interval (CI), 0.57–0.86, p < 0.01) and 4.7 mg/dl, respectively. For Alb, AUC and cutoff value were 0.68 (95 % CI, 0.53–0.82, p < 0.05) and 2.7 g/dl, respectively. A significant difference was seen in voriconazole trough concentration between patients with hepatotoxicity and those without (5.69 μg/ml vs 3.0 μg/ml, p < 0.001). CONCLUSION: Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance. We propose that early measurement of voriconazole concentration before the plateau phase will lead to avoidance of a toxic voriconazole level in patients with elevated CRP level and hypoalbuminemia, although further studies are needed to confirm our findings. BioMed Central 2016-04-19 /pmc/articles/PMC4835838/ /pubmed/27096102 http://dx.doi.org/10.1186/s40780-016-0044-9 Text en © Dote et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Dote, Satoshi
Sawai, Maki
Nozaki, Ayumu
Naruhashi, Kazumasa
Kobayashi, Yuka
Nakanishi, Hirokazu
A retrospective analysis of patient-specific factors on voriconazole clearance
title A retrospective analysis of patient-specific factors on voriconazole clearance
title_full A retrospective analysis of patient-specific factors on voriconazole clearance
title_fullStr A retrospective analysis of patient-specific factors on voriconazole clearance
title_full_unstemmed A retrospective analysis of patient-specific factors on voriconazole clearance
title_short A retrospective analysis of patient-specific factors on voriconazole clearance
title_sort retrospective analysis of patient-specific factors on voriconazole clearance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835838/
https://www.ncbi.nlm.nih.gov/pubmed/27096102
http://dx.doi.org/10.1186/s40780-016-0044-9
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