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Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease
Platelets are produced by hematopoietic stem cells via megakaryocytes in the bone marrow and play a critical role in hemostasis. The aim of this study was to develop a new platelet model based on the thrombopoiesis and platelet life‐cycle by a quantitative systems pharmacology modeling approach, whi...
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/PMC8129717/ https://www.ncbi.nlm.nih.gov/pubmed/33797208 http://dx.doi.org/10.1002/psp4.12623 |
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author | Shimizu, Ryosuke Katsube, Takayuki Wajima, Toshihiro |
author_facet | Shimizu, Ryosuke Katsube, Takayuki Wajima, Toshihiro |
author_sort | Shimizu, Ryosuke |
collection | PubMed |
description | Platelets are produced by hematopoietic stem cells via megakaryocytes in the bone marrow and play a critical role in hemostasis. The aim of this study was to develop a new platelet model based on the thrombopoiesis and platelet life‐cycle by a quantitative systems pharmacology modeling approach, which could describe changes in platelet count profiles in platelet‐related diseases and drug intervention. The proposed platelet model consists of 44 components. The model was applied to thrombopoiesis of a thrombopoietin receptor agonist, lusutrombopag. It could well describe the observed platelet count profiles after administration of lusutrombopag for both healthy subjects and patients with chronic liver disease and thrombocytopenia. This model should be useful for understanding the disease progression of platelet‐related conditions, such as thrombocytopenia and for predicting platelet count profiles in various disease situations related to platelets and drug administration in drug development. |
format | Online Article Text |
id | pubmed-8129717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81297172021-05-21 Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease Shimizu, Ryosuke Katsube, Takayuki Wajima, Toshihiro CPT Pharmacometrics Syst Pharmacol Research Platelets are produced by hematopoietic stem cells via megakaryocytes in the bone marrow and play a critical role in hemostasis. The aim of this study was to develop a new platelet model based on the thrombopoiesis and platelet life‐cycle by a quantitative systems pharmacology modeling approach, which could describe changes in platelet count profiles in platelet‐related diseases and drug intervention. The proposed platelet model consists of 44 components. The model was applied to thrombopoiesis of a thrombopoietin receptor agonist, lusutrombopag. It could well describe the observed platelet count profiles after administration of lusutrombopag for both healthy subjects and patients with chronic liver disease and thrombocytopenia. This model should be useful for understanding the disease progression of platelet‐related conditions, such as thrombocytopenia and for predicting platelet count profiles in various disease situations related to platelets and drug administration in drug development. John Wiley and Sons Inc. 2021-05-03 2021-05 /pmc/articles/PMC8129717/ /pubmed/33797208 http://dx.doi.org/10.1002/psp4.12623 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 | Research Shimizu, Ryosuke Katsube, Takayuki Wajima, Toshihiro Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
title | Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
title_full | Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
title_fullStr | Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
title_full_unstemmed | Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
title_short | Quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
title_sort | quantitative systems pharmacology model of thrombopoiesis and platelet life‐cycle, and its application to thrombocytopenia based on chronic liver disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129717/ https://www.ncbi.nlm.nih.gov/pubmed/33797208 http://dx.doi.org/10.1002/psp4.12623 |
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