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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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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. |
format | Online Article Text |
id | pubmed-4835838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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