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End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor
Model‐informed drug development (MIDD) is critical in all stages of the drug‐development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end‐to‐end development of ertugliflozin, a sod...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213419/ https://www.ncbi.nlm.nih.gov/pubmed/33932126 http://dx.doi.org/10.1002/psp4.12633 |
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author | Fediuk, Daryl J. Nucci, Gianluca Dawra, Vikas K. Callegari, Ernesto Zhou, Susan Musante, Cynthia J. Liang, Yali Sweeney, Kevin Sahasrabudhe, Vaishali |
author_facet | Fediuk, Daryl J. Nucci, Gianluca Dawra, Vikas K. Callegari, Ernesto Zhou, Susan Musante, Cynthia J. Liang, Yali Sweeney, Kevin Sahasrabudhe, Vaishali |
author_sort | Fediuk, Daryl J. |
collection | PubMed |
description | Model‐informed drug development (MIDD) is critical in all stages of the drug‐development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end‐to‐end development of ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose–response relationships, (2) dose–response modeling and model‐based meta‐analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose‐proportionality and the impact of uridine 5'‐diphospho‐glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically‐based PK modeling to assess the risk of UGT‐mediated drug–drug interactions. These end‐to‐end MIDD approaches for ertugliflozin facilitated decision making, resulted in time/cost savings, and supported registration and labeling. |
format | Online Article Text |
id | pubmed-8213419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82134192021-06-28 End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor Fediuk, Daryl J. Nucci, Gianluca Dawra, Vikas K. Callegari, Ernesto Zhou, Susan Musante, Cynthia J. Liang, Yali Sweeney, Kevin Sahasrabudhe, Vaishali CPT Pharmacometrics Syst Pharmacol Reviews Model‐informed drug development (MIDD) is critical in all stages of the drug‐development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end‐to‐end development of ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose–response relationships, (2) dose–response modeling and model‐based meta‐analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose‐proportionality and the impact of uridine 5'‐diphospho‐glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically‐based PK modeling to assess the risk of UGT‐mediated drug–drug interactions. These end‐to‐end MIDD approaches for ertugliflozin facilitated decision making, resulted in time/cost savings, and supported registration and labeling. John Wiley and Sons Inc. 2021-05-15 2021-06 /pmc/articles/PMC8213419/ /pubmed/33932126 http://dx.doi.org/10.1002/psp4.12633 Text en © 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Reviews Fediuk, Daryl J. Nucci, Gianluca Dawra, Vikas K. Callegari, Ernesto Zhou, Susan Musante, Cynthia J. Liang, Yali Sweeney, Kevin Sahasrabudhe, Vaishali End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
title | End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
title_full | End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
title_fullStr | End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
title_full_unstemmed | End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
title_short | End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
title_sort | end‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213419/ https://www.ncbi.nlm.nih.gov/pubmed/33932126 http://dx.doi.org/10.1002/psp4.12633 |
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