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Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models
BACKGROUND: To facilitate new drug development, physiologically-based pharmacokinetic (PBPK) modeling methods receive growing attention as a tool to fully understand and predict complex pharmacokinetic phenomena. As the number of parameters to reproduce physiological functions tend to be large in PB...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852065/ https://www.ncbi.nlm.nih.gov/pubmed/24555857 http://dx.doi.org/10.1186/1752-0509-7-S3-S3 |
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author | Yoshida, Kenta Maeda, Kazuya Kusuhara, Hiroyuki Konagaya, Akihiko |
author_facet | Yoshida, Kenta Maeda, Kazuya Kusuhara, Hiroyuki Konagaya, Akihiko |
author_sort | Yoshida, Kenta |
collection | PubMed |
description | BACKGROUND: To facilitate new drug development, physiologically-based pharmacokinetic (PBPK) modeling methods receive growing attention as a tool to fully understand and predict complex pharmacokinetic phenomena. As the number of parameters to reproduce physiological functions tend to be large in PBPK models, efficient parameter estimation methods are essential. We have successfully applied a recently developed algorithm to estimate a feasible solution space, called Cluster Newton Method (CNM), to reveal the cause of irinotecan pharmacokinetic alterations in two cancer patient groups. RESULTS: After improvements in the original CNM algorithm to maintain parameter diversities, a feasible solution space was successfully estimated for 55 or 56 parameters in the irinotecan PBPK model, within ten iterations, 3000 virtual samples, and in 15 minutes (Intel Xeon E5-1620 3.60GHz × 1 or Intel Core i7-870 2.93GHz × 1). Control parameters or parameter correlations were clarified after the parameter estimation processes. Possible causes in the irinotecan pharmacokinetic alterations were suggested, but they were not conclusive. CONCLUSIONS: Application of CNM achieved a feasible solution space by solving inverse problems of a system containing ordinary differential equations (ODEs). This method may give us reliable insights into other complicated phenomena, which have a large number of parameters to estimate, under limited information. It is also helpful to design prospective studies for further investigation of phenomena of interest. |
format | Online Article Text |
id | pubmed-3852065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38520652013-12-20 Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models Yoshida, Kenta Maeda, Kazuya Kusuhara, Hiroyuki Konagaya, Akihiko BMC Syst Biol Research BACKGROUND: To facilitate new drug development, physiologically-based pharmacokinetic (PBPK) modeling methods receive growing attention as a tool to fully understand and predict complex pharmacokinetic phenomena. As the number of parameters to reproduce physiological functions tend to be large in PBPK models, efficient parameter estimation methods are essential. We have successfully applied a recently developed algorithm to estimate a feasible solution space, called Cluster Newton Method (CNM), to reveal the cause of irinotecan pharmacokinetic alterations in two cancer patient groups. RESULTS: After improvements in the original CNM algorithm to maintain parameter diversities, a feasible solution space was successfully estimated for 55 or 56 parameters in the irinotecan PBPK model, within ten iterations, 3000 virtual samples, and in 15 minutes (Intel Xeon E5-1620 3.60GHz × 1 or Intel Core i7-870 2.93GHz × 1). Control parameters or parameter correlations were clarified after the parameter estimation processes. Possible causes in the irinotecan pharmacokinetic alterations were suggested, but they were not conclusive. CONCLUSIONS: Application of CNM achieved a feasible solution space by solving inverse problems of a system containing ordinary differential equations (ODEs). This method may give us reliable insights into other complicated phenomena, which have a large number of parameters to estimate, under limited information. It is also helpful to design prospective studies for further investigation of phenomena of interest. BioMed Central 2013-10-16 /pmc/articles/PMC3852065/ /pubmed/24555857 http://dx.doi.org/10.1186/1752-0509-7-S3-S3 Text en Copyright © 2013 Yoshida et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Yoshida, Kenta Maeda, Kazuya Kusuhara, Hiroyuki Konagaya, Akihiko Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
title | Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
title_full | Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
title_fullStr | Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
title_full_unstemmed | Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
title_short | Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
title_sort | estimation of feasible solution space using cluster newton method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852065/ https://www.ncbi.nlm.nih.gov/pubmed/24555857 http://dx.doi.org/10.1186/1752-0509-7-S3-S3 |
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