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

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_1F77B194CA9D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children.
Journal
Pharmaceutics
Author(s)
Goutelle S., Thoma Y., Buffet R., Philippe M., Buclin T., Guidi M., Csajka C.
ISSN
1999-4923 (Print)
ISSN-L
1999-4923
Publication state
Published
Issued date
01/10/2022
Peer-reviewed
Oui
Volume
14
Number
10
Pages
2107
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Keywords
Pharmaceutical Science, busulfan, hematopoietic stem cell transplantation, model-informed precision dosing, oncology, pediatrics, population pharmacokinetics, therapeutic drug monitoring
Pubmed
Web of science
Open Access
Yes
Create date
25/10/2022 7:11
Last modification date
02/02/2023 7:08
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