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Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction

Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-vetted models can be...

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Autores principales: Lu, Jingtao, Goldsmith, Michael-Rock, Grulke, Christopher M., Chang, Daniel T., Brooks, Raina D., Leonard, Jeremy A., Phillips, Martin B., Hypes, Ethan D., Fair, Matthew J., Tornero-Velez, Rogelio, Johnson, Jeffre, Dary, Curtis C., Tan, Yu-Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752336/
https://www.ncbi.nlm.nih.gov/pubmed/26871706
http://dx.doi.org/10.1371/journal.pcbi.1004495
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author Lu, Jingtao
Goldsmith, Michael-Rock
Grulke, Christopher M.
Chang, Daniel T.
Brooks, Raina D.
Leonard, Jeremy A.
Phillips, Martin B.
Hypes, Ethan D.
Fair, Matthew J.
Tornero-Velez, Rogelio
Johnson, Jeffre
Dary, Curtis C.
Tan, Yu-Mei
author_facet Lu, Jingtao
Goldsmith, Michael-Rock
Grulke, Christopher M.
Chang, Daniel T.
Brooks, Raina D.
Leonard, Jeremy A.
Phillips, Martin B.
Hypes, Ethan D.
Fair, Matthew J.
Tornero-Velez, Rogelio
Johnson, Jeffre
Dary, Curtis C.
Tan, Yu-Mei
author_sort Lu, Jingtao
collection PubMed
description Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-vetted models can be a great resource for the construction of models pertaining to new chemicals. A PBPK knowledgebase was compiled and developed from existing PBPK-related articles and used to develop new models. From 2,039 PBPK-related articles published between 1977 and 2013, 307 unique chemicals were identified for use as the basis of our knowledgebase. Keywords related to species, gender, developmental stages, and organs were analyzed from the articles within the PBPK knowledgebase. A correlation matrix of the 307 chemicals in the PBPK knowledgebase was calculated based on pharmacokinetic-relevant molecular descriptors. Chemicals in the PBPK knowledgebase were ranked based on their correlation toward ethylbenzene and gefitinib. Next, multiple chemicals were selected to represent exact matches, close analogues, or non-analogues of the target case study chemicals. Parameters, equations, or experimental data relevant to existing models for these chemicals and their analogues were used to construct new models, and model predictions were compared to observed values. This compiled knowledgebase provides a chemical structure-based approach for identifying PBPK models relevant to other chemical entities. Using suitable correlation metrics, we demonstrated that models of chemical analogues in the PBPK knowledgebase can guide the construction of PBPK models for other chemicals.
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spelling pubmed-47523362016-02-26 Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction Lu, Jingtao Goldsmith, Michael-Rock Grulke, Christopher M. Chang, Daniel T. Brooks, Raina D. Leonard, Jeremy A. Phillips, Martin B. Hypes, Ethan D. Fair, Matthew J. Tornero-Velez, Rogelio Johnson, Jeffre Dary, Curtis C. Tan, Yu-Mei PLoS Comput Biol Research Article Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-vetted models can be a great resource for the construction of models pertaining to new chemicals. A PBPK knowledgebase was compiled and developed from existing PBPK-related articles and used to develop new models. From 2,039 PBPK-related articles published between 1977 and 2013, 307 unique chemicals were identified for use as the basis of our knowledgebase. Keywords related to species, gender, developmental stages, and organs were analyzed from the articles within the PBPK knowledgebase. A correlation matrix of the 307 chemicals in the PBPK knowledgebase was calculated based on pharmacokinetic-relevant molecular descriptors. Chemicals in the PBPK knowledgebase were ranked based on their correlation toward ethylbenzene and gefitinib. Next, multiple chemicals were selected to represent exact matches, close analogues, or non-analogues of the target case study chemicals. Parameters, equations, or experimental data relevant to existing models for these chemicals and their analogues were used to construct new models, and model predictions were compared to observed values. This compiled knowledgebase provides a chemical structure-based approach for identifying PBPK models relevant to other chemical entities. Using suitable correlation metrics, we demonstrated that models of chemical analogues in the PBPK knowledgebase can guide the construction of PBPK models for other chemicals. Public Library of Science 2016-02-12 /pmc/articles/PMC4752336/ /pubmed/26871706 http://dx.doi.org/10.1371/journal.pcbi.1004495 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Lu, Jingtao
Goldsmith, Michael-Rock
Grulke, Christopher M.
Chang, Daniel T.
Brooks, Raina D.
Leonard, Jeremy A.
Phillips, Martin B.
Hypes, Ethan D.
Fair, Matthew J.
Tornero-Velez, Rogelio
Johnson, Jeffre
Dary, Curtis C.
Tan, Yu-Mei
Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction
title Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction
title_full Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction
title_fullStr Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction
title_full_unstemmed Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction
title_short Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction
title_sort developing a physiologically-based pharmacokinetic model knowledgebase in support of provisional model construction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752336/
https://www.ncbi.nlm.nih.gov/pubmed/26871706
http://dx.doi.org/10.1371/journal.pcbi.1004495
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