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Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections
Rezafungin is a novel antifungal agent of the echinocandin class with potent activity against species of Candida and Aspergillus, including subsets of resistant strains, and Pneumocystis jirovecii. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522775/ https://www.ncbi.nlm.nih.gov/pubmed/34398673 http://dx.doi.org/10.1128/AAC.00842-21 |
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author | Rubino, Christopher M. Flanagan, Shawn |
author_facet | Rubino, Christopher M. Flanagan, Shawn |
author_sort | Rubino, Christopher M. |
collection | PubMed |
description | Rezafungin is a novel antifungal agent of the echinocandin class with potent activity against species of Candida and Aspergillus, including subsets of resistant strains, and Pneumocystis jirovecii. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize the disposition of rezafungin in plasma following intravenous (IV) administration in healthy volunteers and in patients with candidemia and/or invasive candidiasis. The population PK model was based on a previous model from phase 1 data; formal covariate analyses were conducted to identify any relationships between subject characteristics and rezafungin PK variability. A four-compartment model with linear elimination and zero-order drug input provided a robust fit to the pooled data. Several statistically significant relationships between subject descriptors (sex, infection status, serum albumin, and body surface area [BSA]) and rezafungin PK parameters were identified, but none were deemed clinically relevant. Previous dose justification analyses conducted using data from phase 1 subjects alone are expected to remain appropriate. The final model provided a precise and unbiased fit to the observed concentrations and can be used to reliably predict rezafungin PK in infected patients. |
format | Online Article Text |
id | pubmed-8522775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-85227752021-10-20 Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections Rubino, Christopher M. Flanagan, Shawn Antimicrob Agents Chemother Pharmacology Rezafungin is a novel antifungal agent of the echinocandin class with potent activity against species of Candida and Aspergillus, including subsets of resistant strains, and Pneumocystis jirovecii. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize the disposition of rezafungin in plasma following intravenous (IV) administration in healthy volunteers and in patients with candidemia and/or invasive candidiasis. The population PK model was based on a previous model from phase 1 data; formal covariate analyses were conducted to identify any relationships between subject characteristics and rezafungin PK variability. A four-compartment model with linear elimination and zero-order drug input provided a robust fit to the pooled data. Several statistically significant relationships between subject descriptors (sex, infection status, serum albumin, and body surface area [BSA]) and rezafungin PK parameters were identified, but none were deemed clinically relevant. Previous dose justification analyses conducted using data from phase 1 subjects alone are expected to remain appropriate. The final model provided a precise and unbiased fit to the observed concentrations and can be used to reliably predict rezafungin PK in infected patients. American Society for Microbiology 2021-10-18 /pmc/articles/PMC8522775/ /pubmed/34398673 http://dx.doi.org/10.1128/AAC.00842-21 Text en Copyright © 2021 Rubino and Flanagan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Pharmacology Rubino, Christopher M. Flanagan, Shawn Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections |
title | Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections |
title_full | Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections |
title_fullStr | Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections |
title_full_unstemmed | Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections |
title_short | Population Pharmacokinetics of Rezafungin in Patients with Fungal Infections |
title_sort | population pharmacokinetics of rezafungin in patients with fungal infections |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522775/ https://www.ncbi.nlm.nih.gov/pubmed/34398673 http://dx.doi.org/10.1128/AAC.00842-21 |
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