Cargando…
A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50)
The half-maximal inhibitory concentration IC[Image: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Hum...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731310/ https://www.ncbi.nlm.nih.gov/pubmed/23936323 http://dx.doi.org/10.1371/journal.pone.0069301 |
_version_ | 1782279144785051648 |
---|---|
author | Zhang, Hui Holden-Wiltse, Jeanne Wang, Jiong Liang, Hua |
author_facet | Zhang, Hui Holden-Wiltse, Jeanne Wang, Jiong Liang, Hua |
author_sort | Zhang, Hui |
collection | PubMed |
description | The half-maximal inhibitory concentration IC[Image: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developing resistance to antiviral drugs show that the dose response curve may not be monotonic. Traditional models can fail for nonmonotonic data and ignore observations that may be of biologic significance. Therefore, we propose a nonparametric model to describe the dose response relationship and fit the curve using local polynomial regression. The nonparametric approach is shown to be promising especially for estimating the IC[Image: see text] of some HIV inhibitory drugs, in which there is a dose-dependent stimulation of response for mutant strains. This model strategy may be applicable to general pharmacologic, toxicologic, or other biomedical data that exhibits a nonmonotonic dose response relationship for which traditional parametric models fail. |
format | Online Article Text |
id | pubmed-3731310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37313102013-08-09 A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50) Zhang, Hui Holden-Wiltse, Jeanne Wang, Jiong Liang, Hua PLoS One Research Article The half-maximal inhibitory concentration IC[Image: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developing resistance to antiviral drugs show that the dose response curve may not be monotonic. Traditional models can fail for nonmonotonic data and ignore observations that may be of biologic significance. Therefore, we propose a nonparametric model to describe the dose response relationship and fit the curve using local polynomial regression. The nonparametric approach is shown to be promising especially for estimating the IC[Image: see text] of some HIV inhibitory drugs, in which there is a dose-dependent stimulation of response for mutant strains. This model strategy may be applicable to general pharmacologic, toxicologic, or other biomedical data that exhibits a nonmonotonic dose response relationship for which traditional parametric models fail. Public Library of Science 2013-08-01 /pmc/articles/PMC3731310/ /pubmed/23936323 http://dx.doi.org/10.1371/journal.pone.0069301 Text en © 2013 Zhang 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, Hui Holden-Wiltse, Jeanne Wang, Jiong Liang, Hua A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50) |
title | A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50)
|
title_full | A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50)
|
title_fullStr | A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50)
|
title_full_unstemmed | A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50)
|
title_short | A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC(50)
|
title_sort | strategy to model nonmonotonic dose-response curve and estimate ic(50) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731310/ https://www.ncbi.nlm.nih.gov/pubmed/23936323 http://dx.doi.org/10.1371/journal.pone.0069301 |
work_keys_str_mv | AT zhanghui astrategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT holdenwiltsejeanne astrategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT wangjiong astrategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT lianghua astrategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT zhanghui strategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT holdenwiltsejeanne strategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT wangjiong strategytomodelnonmonotonicdoseresponsecurveandestimateic50 AT lianghua strategytomodelnonmonotonicdoseresponsecurveandestimateic50 |