Understanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling

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dc.contributor.authorCortes-Rios, Javiera
dc.contributor.authorRodriguez-Fernandez, Maria
dc.date.accessioned2025-01-20T20:16:22Z
dc.date.available2025-01-20T20:16:22Z
dc.date.issued2023
dc.description.abstractChronopharmacology 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.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fendo.2023.1110459
dc.identifier.issn1664-2392
dc.identifier.urihttps://doi.org/10.3389/fendo.2023.1110459
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92325
dc.identifier.wosidWOS:000951026100001
dc.language.isoen
dc.revistaFrontiers in endocrinology
dc.rightsacceso restringido
dc.subjectchronopharmacology
dc.subjecthypertension
dc.subjectmathematical modeling
dc.subjectblood pressure
dc.subjectcircadian rhythm
dc.subjectvalsartan
dc.subjectaspirin
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleUnderstanding the dosing-time-dependent antihypertensive effect of valsartan and aspirin through mathematical modeling
dc.typeartículo
dc.volumen14
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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