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Isavuconazole Pharmacokinetics and Pharmacodynamics in Children
Isavuconazole is a broad-spectrum azole anti-fungal not yet approved in children. We conducted a retrospective, single-center review of isavuconazole use and routine therapeutic drug monitoring in pediatric patients, extracting demographic, dosing, concentration, mortality and hepatoxicity data. We...
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/PMC9865364/ https://www.ncbi.nlm.nih.gov/pubmed/36678704 http://dx.doi.org/10.3390/pharmaceutics15010075 |
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author | Elhence, Hirsh Mongkolrattanothai, Kanokporn Mohandas, Sindhu Neely, Michael N. |
author_facet | Elhence, Hirsh Mongkolrattanothai, Kanokporn Mohandas, Sindhu Neely, Michael N. |
author_sort | Elhence, Hirsh |
collection | PubMed |
description | Isavuconazole is a broad-spectrum azole anti-fungal not yet approved in children. We conducted a retrospective, single-center review of isavuconazole use and routine therapeutic drug monitoring in pediatric patients, extracting demographic, dosing, concentration, mortality and hepatoxicity data. We constructed a nonparametric population model using Pmetrics. Of 26 patients, 19 (73%) were male. The mean (SD) age and weight were 12.7 (5.5) years and 50.9 (26.8) kg. Eighty percent received between 9.7 and 10.6 mg/kg per dose. Ten (38%) subjects had proven fungal disease and eight (31%) had probable disease, mostly with Candida and Aspergillus spp. The predicted steady-state isavuconazole concentrations in our patients were similar to previous reports in children and adults, and simulations with the proposed dosing of 10 mg/kg/dose every 8 h for 2 days followed by once daily maintenance matched effective adult exposures. Attributable mortality (5 of 11 deaths) was associated with steady-state daily AUC < 60 mg∗h/L and higher AST/ALT with trough concentrations > 5 mg/L. Neither dose nor trough alone correlated well with AUC, but AUC can be estimated with one sample 10 h after the first maintenance dose or a trough concentration, if combined with a Bayesian approach or a peak and trough without a Bayesian approach. |
format | Online Article Text |
id | pubmed-9865364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98653642023-01-22 Isavuconazole Pharmacokinetics and Pharmacodynamics in Children Elhence, Hirsh Mongkolrattanothai, Kanokporn Mohandas, Sindhu Neely, Michael N. Pharmaceutics Article Isavuconazole is a broad-spectrum azole anti-fungal not yet approved in children. We conducted a retrospective, single-center review of isavuconazole use and routine therapeutic drug monitoring in pediatric patients, extracting demographic, dosing, concentration, mortality and hepatoxicity data. We constructed a nonparametric population model using Pmetrics. Of 26 patients, 19 (73%) were male. The mean (SD) age and weight were 12.7 (5.5) years and 50.9 (26.8) kg. Eighty percent received between 9.7 and 10.6 mg/kg per dose. Ten (38%) subjects had proven fungal disease and eight (31%) had probable disease, mostly with Candida and Aspergillus spp. The predicted steady-state isavuconazole concentrations in our patients were similar to previous reports in children and adults, and simulations with the proposed dosing of 10 mg/kg/dose every 8 h for 2 days followed by once daily maintenance matched effective adult exposures. Attributable mortality (5 of 11 deaths) was associated with steady-state daily AUC < 60 mg∗h/L and higher AST/ALT with trough concentrations > 5 mg/L. Neither dose nor trough alone correlated well with AUC, but AUC can be estimated with one sample 10 h after the first maintenance dose or a trough concentration, if combined with a Bayesian approach or a peak and trough without a Bayesian approach. MDPI 2022-12-26 /pmc/articles/PMC9865364/ /pubmed/36678704 http://dx.doi.org/10.3390/pharmaceutics15010075 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 Elhence, Hirsh Mongkolrattanothai, Kanokporn Mohandas, Sindhu Neely, Michael N. Isavuconazole Pharmacokinetics and Pharmacodynamics in Children |
title | Isavuconazole Pharmacokinetics and Pharmacodynamics in Children |
title_full | Isavuconazole Pharmacokinetics and Pharmacodynamics in Children |
title_fullStr | Isavuconazole Pharmacokinetics and Pharmacodynamics in Children |
title_full_unstemmed | Isavuconazole Pharmacokinetics and Pharmacodynamics in Children |
title_short | Isavuconazole Pharmacokinetics and Pharmacodynamics in Children |
title_sort | isavuconazole pharmacokinetics and pharmacodynamics in children |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865364/ https://www.ncbi.nlm.nih.gov/pubmed/36678704 http://dx.doi.org/10.3390/pharmaceutics15010075 |
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