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Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling
Chronopharmacology of arterial hypertension impacts the long-term cardiovascular risk of hypertensive subjects. Therefore, clinical and computational studies have proposed optimizing antihypertensive medications’ dosing time (Ta). However, the causes and mechanisms underlying the Ta-dependency antih...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031009/ https://www.ncbi.nlm.nih.gov/pubmed/36967780 http://dx.doi.org/10.3389/fendo.2023.1110459 |
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author | Cortés-Ríos, Javiera Rodriguez-Fernandez, Maria |
author_facet | Cortés-Ríos, Javiera Rodriguez-Fernandez, Maria |
author_sort | Cortés-Ríos, Javiera |
collection | PubMed |
description | Chronopharmacology of arterial hypertension impacts the long-term cardiovascular risk of hypertensive subjects. Therefore, clinical and computational studies have proposed optimizing antihypertensive medications’ dosing time (Ta). However, the causes and mechanisms underlying the Ta-dependency antihypertensive effect have not been elucidated. Here we propose using a Ta- dependent effect model to understand and predict the antihypertensive effect of valsartan and aspirin throughout the day in subjects with grade I or II essential hypertension. The model based on physiological regulation mechanisms includes a periodic function for each parameter that changes significantly after treatment. Circadian variations of parameters depending on the dosing time allowed the determination of regulation mechanisms dependent on the circadian rhythm that were most relevant for the action of each drug. In the case of valsartan, it is the regulation of vasodilation and systemic vascular resistance. In the case of aspirin, the antithrombotic effect generates changes in the sensitivity of systemic vascular resistance and heart rate to changes in physical activity. Dosing time-dependent models predict a more significant effect on systemic vascular resistance and blood pressure when administering valsartan or aspirin at bedtime. However, circadian dependence on the regulation mechanisms showed different sensitivity of their circadian parameters and shapes of functions, presenting different phase shifts and amplitude. Therefore, different mechanisms of action and pharmacokinetic properties of each drug can generate different profiles of Ta-dependence of antihypertensive effect and optimal dosing times. |
format | Online Article Text |
id | pubmed-10031009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100310092023-03-23 Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling Cortés-Ríos, Javiera Rodriguez-Fernandez, Maria Front Endocrinol (Lausanne) Endocrinology Chronopharmacology of arterial hypertension impacts the long-term cardiovascular risk of hypertensive subjects. Therefore, clinical and computational studies have proposed optimizing antihypertensive medications’ dosing time (Ta). However, the causes and mechanisms underlying the Ta-dependency antihypertensive effect have not been elucidated. Here we propose using a Ta- dependent effect model to understand and predict the antihypertensive effect of valsartan and aspirin throughout the day in subjects with grade I or II essential hypertension. The model based on physiological regulation mechanisms includes a periodic function for each parameter that changes significantly after treatment. Circadian variations of parameters depending on the dosing time allowed the determination of regulation mechanisms dependent on the circadian rhythm that were most relevant for the action of each drug. In the case of valsartan, it is the regulation of vasodilation and systemic vascular resistance. In the case of aspirin, the antithrombotic effect generates changes in the sensitivity of systemic vascular resistance and heart rate to changes in physical activity. Dosing time-dependent models predict a more significant effect on systemic vascular resistance and blood pressure when administering valsartan or aspirin at bedtime. However, circadian dependence on the regulation mechanisms showed different sensitivity of their circadian parameters and shapes of functions, presenting different phase shifts and amplitude. Therefore, different mechanisms of action and pharmacokinetic properties of each drug can generate different profiles of Ta-dependence of antihypertensive effect and optimal dosing times. Frontiers Media S.A. 2023-03-08 /pmc/articles/PMC10031009/ /pubmed/36967780 http://dx.doi.org/10.3389/fendo.2023.1110459 Text en Copyright © 2023 Cortés-Ríos and Rodriguez-Fernandez https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Cortés-Ríos, Javiera Rodriguez-Fernandez, Maria Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
title | Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
title_full | Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
title_fullStr | Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
title_full_unstemmed | Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
title_short | Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
title_sort | understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031009/ https://www.ncbi.nlm.nih.gov/pubmed/36967780 http://dx.doi.org/10.3389/fendo.2023.1110459 |
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