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Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children
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 cr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611936/ https://www.ncbi.nlm.nih.gov/pubmed/36297541 http://dx.doi.org/10.3390/pharmaceutics14102107 |
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author | Goutelle, Sylvain Thoma, Yann Buffet, Roxane Philippe, Michael Buclin, Thierry Guidi, Monia Csajka, Chantal |
author_facet | Goutelle, Sylvain Thoma, Yann Buffet, Roxane Philippe, Michael Buclin, Thierry Guidi, Monia Csajka, Chantal |
author_sort | Goutelle, Sylvain |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9611936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96119362022-10-28 Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children Goutelle, Sylvain Thoma, Yann Buffet, Roxane Philippe, Michael Buclin, Thierry Guidi, Monia Csajka, Chantal Pharmaceutics Article 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. MDPI 2022-10-01 /pmc/articles/PMC9611936/ /pubmed/36297541 http://dx.doi.org/10.3390/pharmaceutics14102107 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Goutelle, Sylvain Thoma, Yann Buffet, Roxane Philippe, Michael Buclin, Thierry Guidi, Monia Csajka, Chantal Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children |
title | Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children |
title_full | Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children |
title_fullStr | Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children |
title_full_unstemmed | Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children |
title_short | Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children |
title_sort | implementation and cross-validation of a pharmacokinetic model for precision dosing of busulfan in hematopoietic stem cell transplanted children |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611936/ https://www.ncbi.nlm.nih.gov/pubmed/36297541 http://dx.doi.org/10.3390/pharmaceutics14102107 |
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