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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...

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Autores principales: Rubino, Christopher M., Flanagan, Shawn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
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.
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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.
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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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