Pharmacokinetic modelling of caspofungin to develop an extended dosing regimen in paediatric patients.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
28 07 2022
28 07 2022
Historique:
received:
24
01
2022
accepted:
16
05
2022
pubmed:
14
6
2022
medline:
2
8
2022
entrez:
13
6
2022
Statut:
ppublish
Résumé
Echinocandins are commonly used in treatment and prophylaxis of invasive fungal diseases. Intravenous daily dosing for prophylaxis in the outpatient setting can however become a hurdle for adequate compliance in the paediatric population. Simulations were performed to assess extended twice-weekly dosing for antifungal prophylaxis using caspofungin. A population pharmacokinetic model was developed based on previously published data from children aged 3 months to 17 years. Using the final model, Monte Carlo simulations were performed to assess the dose needed for adequate exposure in a twice-weekly setting. Mean weekly AUC0-24 h/MIC together with reported AUC0-24 h from previously reported paediatric trials were used to guide adequate exposure. A two-compartment model with linear elimination and allometric scaling using fixed exponents was found most adequate to describe the given paediatric populations. Simulations showed that a 200 mg/m2 twice-weekly regimen with maximal 200 mg total dose should result in exposures matching registered daily dosing as well as commonly used pharmacokinetic/pharmacodynamic targets.
Sections du résumé
BACKGROUND
Echinocandins are commonly used in treatment and prophylaxis of invasive fungal diseases. Intravenous daily dosing for prophylaxis in the outpatient setting can however become a hurdle for adequate compliance in the paediatric population.
OBJECTIVES
Simulations were performed to assess extended twice-weekly dosing for antifungal prophylaxis using caspofungin.
METHODS
A population pharmacokinetic model was developed based on previously published data from children aged 3 months to 17 years. Using the final model, Monte Carlo simulations were performed to assess the dose needed for adequate exposure in a twice-weekly setting. Mean weekly AUC0-24 h/MIC together with reported AUC0-24 h from previously reported paediatric trials were used to guide adequate exposure.
RESULTS AND CONCLUSIONS
A two-compartment model with linear elimination and allometric scaling using fixed exponents was found most adequate to describe the given paediatric populations. Simulations showed that a 200 mg/m2 twice-weekly regimen with maximal 200 mg total dose should result in exposures matching registered daily dosing as well as commonly used pharmacokinetic/pharmacodynamic targets.
Identifiants
pubmed: 35696555
pii: 6607745
doi: 10.1093/jac/dkac182
doi:
Substances chimiques
Antifungal Agents
0
Echinocandins
0
Caspofungin
F0XDI6ZL63
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2209-2216Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.