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Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model
Regulatory agencies currently recommend itraconazole (ITZ) as a strong cytochrome P450 3A (CYP3A) inhibitor for clinical drug–drug interaction (DDI) studies. This work by an International Consortium for Innovation and Quality in Pharmaceutical Development working group (WG) is to develop and verify...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765698/ https://www.ncbi.nlm.nih.gov/pubmed/31215774 http://dx.doi.org/10.1002/psp4.12449 |
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author | Chen, Yuan Cabalu, Tamara D. Callegari, Ernesto Einolf, Heidi Liu, Lichuan Parrott, Neil Peters, Sheila Annie Schuck, Edgar Sharma, Pradeep Tracey, Helen Upreti, Vijay V. Zheng, Ming Zhu, Andy Z.X. Hall, Stephen D. |
author_facet | Chen, Yuan Cabalu, Tamara D. Callegari, Ernesto Einolf, Heidi Liu, Lichuan Parrott, Neil Peters, Sheila Annie Schuck, Edgar Sharma, Pradeep Tracey, Helen Upreti, Vijay V. Zheng, Ming Zhu, Andy Z.X. Hall, Stephen D. |
author_sort | Chen, Yuan |
collection | PubMed |
description | Regulatory agencies currently recommend itraconazole (ITZ) as a strong cytochrome P450 3A (CYP3A) inhibitor for clinical drug–drug interaction (DDI) studies. This work by an International Consortium for Innovation and Quality in Pharmaceutical Development working group (WG) is to develop and verify a mechanistic ITZ physiologically‐based pharmacokinetic model and provide recommendations for optimal DDI study design based on model simulations. To support model development and verification, in vitro and clinical PK data for ITZ and its metabolites were collected from WG member companies. The model predictions of ITZ DDIs with seven different CYP3A substrates were within the guest criteria for 92% of area under the concentration‐time curve ratios and 95% of maximum plasma concentration ratios, thus verifying the model for DDI predictions. The verified model was used to simulate various clinical DDI study scenarios considering formulation, duration of dosing, dose regimen, and food status to recommend the optimal design for maximal inhibitory effect by ITZ. |
format | Online Article Text |
id | pubmed-6765698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67656982019-09-30 Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model Chen, Yuan Cabalu, Tamara D. Callegari, Ernesto Einolf, Heidi Liu, Lichuan Parrott, Neil Peters, Sheila Annie Schuck, Edgar Sharma, Pradeep Tracey, Helen Upreti, Vijay V. Zheng, Ming Zhu, Andy Z.X. Hall, Stephen D. CPT Pharmacometrics Syst Pharmacol Research Regulatory agencies currently recommend itraconazole (ITZ) as a strong cytochrome P450 3A (CYP3A) inhibitor for clinical drug–drug interaction (DDI) studies. This work by an International Consortium for Innovation and Quality in Pharmaceutical Development working group (WG) is to develop and verify a mechanistic ITZ physiologically‐based pharmacokinetic model and provide recommendations for optimal DDI study design based on model simulations. To support model development and verification, in vitro and clinical PK data for ITZ and its metabolites were collected from WG member companies. The model predictions of ITZ DDIs with seven different CYP3A substrates were within the guest criteria for 92% of area under the concentration‐time curve ratios and 95% of maximum plasma concentration ratios, thus verifying the model for DDI predictions. The verified model was used to simulate various clinical DDI study scenarios considering formulation, duration of dosing, dose regimen, and food status to recommend the optimal design for maximal inhibitory effect by ITZ. John Wiley and Sons Inc. 2019-08-07 2019-09 /pmc/articles/PMC6765698/ /pubmed/31215774 http://dx.doi.org/10.1002/psp4.12449 Text en © 2019 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Chen, Yuan Cabalu, Tamara D. Callegari, Ernesto Einolf, Heidi Liu, Lichuan Parrott, Neil Peters, Sheila Annie Schuck, Edgar Sharma, Pradeep Tracey, Helen Upreti, Vijay V. Zheng, Ming Zhu, Andy Z.X. Hall, Stephen D. Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model |
title | Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model |
title_full | Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model |
title_fullStr | Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model |
title_full_unstemmed | Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model |
title_short | Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model |
title_sort | recommendations for the design of clinical drug–drug interaction studies with itraconazole using a mechanistic physiologically‐based pharmacokinetic model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765698/ https://www.ncbi.nlm.nih.gov/pubmed/31215774 http://dx.doi.org/10.1002/psp4.12449 |
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