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Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits
The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standar...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862475/ https://www.ncbi.nlm.nih.gov/pubmed/29561908 http://dx.doi.org/10.1371/journal.pone.0194294 |
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author | Mavroudis, Panteleimon D. Hermes, Helen E. Teutonico, Donato Preuss, Thomas G. Schneckener, Sebastian |
author_facet | Mavroudis, Panteleimon D. Hermes, Helen E. Teutonico, Donato Preuss, Thomas G. Schneckener, Sebastian |
author_sort | Mavroudis, Panteleimon D. |
collection | PubMed |
description | The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standard laboratory animals such as rabbits are tested, and the observed adverse effects are translated to focal species for environmental risk assessments. In that respect, mathematical modelling is becoming increasingly important for evaluating the consequences of pesticides in untested scenarios. In particular, physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) modelling is a well-established methodology used to predict tissue concentrations based on the absorption, distribution, metabolism and excretion of drugs and toxicants. In the present work, a rabbit PBPK/TK model is developed and evaluated with data available from the literature. The model predictions include scenarios of both intravenous (i.v.) and oral (p.o.) administration of small and large compounds. The presented rabbit PBPK/TK model predicts the pharmacokinetics (Cmax, AUC) of the tested compounds with an average 1.7-fold error. This result indicates a good predictive capacity of the model, which enables its use for risk assessment modelling and simulations. |
format | Online Article Text |
id | pubmed-5862475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58624752018-03-28 Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits Mavroudis, Panteleimon D. Hermes, Helen E. Teutonico, Donato Preuss, Thomas G. Schneckener, Sebastian PLoS One Research Article The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standard laboratory animals such as rabbits are tested, and the observed adverse effects are translated to focal species for environmental risk assessments. In that respect, mathematical modelling is becoming increasingly important for evaluating the consequences of pesticides in untested scenarios. In particular, physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) modelling is a well-established methodology used to predict tissue concentrations based on the absorption, distribution, metabolism and excretion of drugs and toxicants. In the present work, a rabbit PBPK/TK model is developed and evaluated with data available from the literature. The model predictions include scenarios of both intravenous (i.v.) and oral (p.o.) administration of small and large compounds. The presented rabbit PBPK/TK model predicts the pharmacokinetics (Cmax, AUC) of the tested compounds with an average 1.7-fold error. This result indicates a good predictive capacity of the model, which enables its use for risk assessment modelling and simulations. Public Library of Science 2018-03-21 /pmc/articles/PMC5862475/ /pubmed/29561908 http://dx.doi.org/10.1371/journal.pone.0194294 Text en © 2018 Mavroudis et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Mavroudis, Panteleimon D. Hermes, Helen E. Teutonico, Donato Preuss, Thomas G. Schneckener, Sebastian Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
title | Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
title_full | Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
title_fullStr | Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
title_full_unstemmed | Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
title_short | Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
title_sort | development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862475/ https://www.ncbi.nlm.nih.gov/pubmed/29561908 http://dx.doi.org/10.1371/journal.pone.0194294 |
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