Administration time-dependent effects of amlodipine on ambulatory blood pressure in patients with essential hypertension

Hermida, Ramón C.; Calvo, Carlos; Ayala, Diana E.; López, José E.; Rodriguez, Marta; Covelo, Manuel

doi:10.1016/j.amjhyper.2005.03.167

Cited by 9 publications

(9 citation statements)

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“…Nifedipine even failed to achieve the therapeutic objective for dipper subjects due to its immediate-release formulation, which is why it is not usually used in the chronic treatment of arterial hypertension but rather in hypertensive crises [ 44 ]. On the other hand, the drug that presented a smaller variation of effect on BP and dipper percentage was amlodipine, which coincides with the nonsignificant differences between different dosing times observed by other authors [ 45 – 48 ]. Finally, studies of lisinopril, ramipril, enalapril, spirapril, valsartan, telmisartan and olmesartan showed a significant improvement in the dipper percentage in bedtime administration, which is consistent with our analyses [ 49 – 61 ].…”

Section: Discussionsupporting

confidence: 88%

Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models

2022

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Blood pressure (BP) follows a circadian variation, increasing during active hours, showing a small postprandial valley and a deeper decrease during sleep. Nighttime reduction of 10–20% relative to daytime BP is defined as a dipper pattern, and a reduction of less than 10%, as a non-dipper pattern. Despite this BP variability, hypertension’s diagnostic criteria and therapeutic objectives are usually based on BP average values. Indeed, studies have shown that chrono-pharmacological optimization significantly reduces long-term cardiovascular risk if a BP dipper pattern is maintained. Changes in the effect of antihypertensive medications can be explained by circadian variations in their pharmacokinetics (PK) and pharmacodynamics (PD). Nevertheless, BP circadian variation has been scarcely included in PK-PD models of antihypertensive medications to date. In this work, we developed PK-PD models that include circadian rhythm to find the optimal dosing time (Ta) of first-line antihypertensive medications for dipper and non-dipper patterns. The parameters of the PK-PD models were estimated using global optimization, and models were selected according to the lowest corrected Akaike information criterion value. Simultaneously, sensitivity and identifiability analysis were performed to determine the relevance of the parameters and establish those that can be estimated. Subsequently, Ta parameters were optimized to maximize the effect on BP average, BP peaks, and sleep-time dip. As a result, all selected models included at least one circadian PK component, and circadian parameters had the highest sensitivity. Furthermore, Ta with which BP>130/80 mmHg and a dip of 10–20% are achieved were proposed when possible. We show that the optimal Ta depends on the therapeutic objective, the medication, and the BP profile. Therefore, our results suggest making chrono-pharmacological recommendations in a personalized way.

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Section: Discussionsupporting

confidence: 88%

Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models

2022

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“…Several trials involving a relatively small number of patients investigated the differential effects of morning versus evening schedules of amlodipine [50][51][52][53], cilnidipine [54], diltiazem [55], isradipine [56,57], nifedipine [58], nisoldipine [59] and nitrendipine [60,61], sometimes producing contrasting findings. Dihydropyridine derivatives seem to reduce BP homogeneously throughout the 24 h, independent of dosing time.…”

Section: Chronotherapy With Calcium Channel Blockersmentioning

confidence: 99%

Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension

Smolensky

Hermida

Ayala

et al. 2010

Blood Pressure Monitoring

146

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There is growing interest on how to best tailor blood pressure (BP)-lowering medications according to the circadian (24 h) BP pattern of individual patients, that is, chronotherapy. Significant and clinically meaningful treatment-time differences in the beneficial and/or adverse effects of at least six different classes of hypertension medications are now known. Generally, calcium channel blockers are more effective with bedtime than morning dosing, and in the case of dihydropyridine derivatives bedtime dosing significantly reduces the risk of edema. Scheduling angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors at bedtime, as opposed to awakening, increases the proportion of patients with properly controlled BP, enhances the sleep-time relative BP decline towards a normal dipping pattern and best reduces urinary albumin excretion, a marker of functional renal status. The chronotherapy of conventional BP-lowering medications entails their correct scheduling with reference to the body's circadian rhythms, not only to achieve control of daytime and night-time systolic and diastolic BP but to normalize the dipping status of the 24 h pattern. Chronotherapy constitutes a cost-effective strategy for enhancing BP control during both nocturnal sleep and daytime activity and for potentially reducing the risk of cardiovascular disease and end-organ injury of the blood vessels and tissue of the heart, brain, kidney, eye and other organs.

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“…In contrast to other groups of antihypertensives, calcium channel blockers (amlodipine [83], cilnidipine [84], diltiazem [85], isradipine [86], nifedipine [87], nisoldipine [88], and nitrendipine [89]) are the only ones that reduce blood pressure equally, regardless of the time of administration.…”

Section: Chronotherapy and Chronopharmaceuticsmentioning

confidence: 99%

Antihypertensives’ Rock around the Clock

Rahić

Tucak

Sirbubalo

et al. 2021

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Although homeostasis is a commonly accepted concept, there is incontrovertible evidence that biological processes and functions are variable and that variability occurs in cycles. In order to explain and understand dysregulation, which has not been embraced by homeostatic principles, the allostatic model has emerged as the first serious challenge to homeostasis, going beyond its homeostatic roots. Circadian rhythm is the predominant variation in the body, and it is a pattern according to which many physiological and pathological events occur. As there is strong experimental and clinical evidence that blood pressure fluctuations undergo circadian rhythm, there is equally strong evidence that targeted time therapy for hypertension provides a better outcome of the disease. The research has gone even further throughout the development and approval process for the use of pulsatile drug release systems, which can be considered as an option for an even more convenient dosage regimen of the medicines needed.

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Administration time-dependent effects of amlodipine on ambulatory blood pressure in patients with essential hypertension

Cited by 9 publications

References 0 publications

Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models

Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models

Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension

Antihypertensives’ Rock around the Clock

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