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