Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children.

Détails

Ressource 1Télécharger: pharmaceutics-14-02107.pdf (1139.72 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_1F77B194CA9D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children.
Périodique
Pharmaceutics
Auteur⸱e⸱s
Goutelle S., Thoma Y., Buffet R., Philippe M., Buclin T., Guidi M., Csajka C.
ISSN
1999-4923 (Print)
ISSN-L
1999-4923
Statut éditorial
Publié
Date de publication
01/10/2022
Peer-reviewed
Oui
Volume
14
Numéro
10
Pages
2107
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Busulfan, a drug used in conditioning prior to hematopoietic stem cell transplantation (HSCT) in children, has a narrow therapeutic margin. The model-informed precision dosing (MIPD) of busulfan is desirable, but there is a lack of validated tools. The objective of this study was to implement and cross-validate a population pharmacokinetic (PK) model in the Tucuxi software for busulfan MIPD in HSCT children. A search of the literature was performed to identify candidate population PK models. The goodness of fit of three selected models was assessed in a dataset of 178 children by computing the mean error (ME) and root-mean-squared error of prediction (RMSE). The best model was implemented in Tucuxi. The individual predicted concentrations, the area under the concentration-time curve (AUC), and dosage requirements were compared between the Tucuxi model and a reference model available in the BestDose software in a subset of 61 children. The model from Paci et al. best fitted the data in the full dataset. In a subset of 61 patients, the predictive performance of Tucuxi and BestDose models was comparable with ME values of 6.4% and -2.5% and RMSE values of 11.4% and 13.6%, respectively. The agreement between the estimated AUC and the predicted dose was good, with 6.6% and 4.9% of the values being out of the 95% limits of agreement, respectively. To conclude, a PK model for busulfan MIPD was cross-validated and is now available in the Tucuxi software.
Mots-clé
Pharmaceutical Science, busulfan, hematopoietic stem cell transplantation, model-informed precision dosing, oncology, pediatrics, population pharmacokinetics, therapeutic drug monitoring
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2022 8:11
Dernière modification de la notice
02/02/2023 8:08
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