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Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction
Herb–drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb–drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between sili...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042458/ https://www.ncbi.nlm.nih.gov/pubmed/24670388 http://dx.doi.org/10.1038/psp.2013.69 |
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author | Brantley, S J Gufford, B T Dua, R Fediuk, D J Graf, T N Scarlett, Y V Frederick, K S Fisher, M B Oberlies, N H Paine, M F |
author_facet | Brantley, S J Gufford, B T Dua, R Fediuk, D J Graf, T N Scarlett, Y V Frederick, K S Fisher, M B Oberlies, N H Paine, M F |
author_sort | Brantley, S J |
collection | PubMed |
description | Herb–drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb–drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160 mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650 mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other herb–drug interactions could facilitate development of guidelines for quantitative prediction of clinically relevant interactions. |
format | Online Article Text |
id | pubmed-4042458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40424582014-06-16 Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction Brantley, S J Gufford, B T Dua, R Fediuk, D J Graf, T N Scarlett, Y V Frederick, K S Fisher, M B Oberlies, N H Paine, M F CPT Pharmacometrics Syst Pharmacol Original Article Herb–drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb–drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160 mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650 mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other herb–drug interactions could facilitate development of guidelines for quantitative prediction of clinically relevant interactions. Nature Publishing Group 2014-03 2014-03-26 /pmc/articles/PMC4042458/ /pubmed/24670388 http://dx.doi.org/10.1038/psp.2013.69 Text en Copyright © 2014 American Society for Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by-nc-nd/3.0/ CPT: Pharmacometrics and Systems Pharmacology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Brantley, S J Gufford, B T Dua, R Fediuk, D J Graf, T N Scarlett, Y V Frederick, K S Fisher, M B Oberlies, N H Paine, M F Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction |
title | Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of
an Herb–Drug Interaction |
title_full | Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of
an Herb–Drug Interaction |
title_fullStr | Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of
an Herb–Drug Interaction |
title_full_unstemmed | Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of
an Herb–Drug Interaction |
title_short | Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of
an Herb–Drug Interaction |
title_sort | physiologically based pharmacokinetic modeling framework for quantitative prediction of
an herb–drug interaction |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042458/ https://www.ncbi.nlm.nih.gov/pubmed/24670388 http://dx.doi.org/10.1038/psp.2013.69 |
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