Ingestion-time differences in the pharmacodynamics of dual-combination hypertension therapies: Systematic review and meta-analysis of published human trials

Hermida-Ayala, Ramón G.; Mojón, Artemio; Fernández, José R.; Smolensky, Michael H.; Hermida, Ramón C.

doi:10.1080/07420528.2021.2005084

Cited by 6 publications

(1 citation statement)

References 59 publications

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“…Recent reviews revealed that evening dosing of ACE inhibitors benazepril, captopril, enalapril, imidapril, lisinopril, perindopril, quinapril, ramipril, spirapril, trandolapril, zofenopril; ARBs irbesartan, candesartan, olmesartan, telmisartan, valsartan; CCBs cilnidipine, isradipine, nifedipine, nisoldipine, verapamil; diuretic torasemide; α-blocker doxazosine; BBs carvedilol and nebivolol among others significantly reduce BP during night rest [9,19]. Better treatment results, adverse effects and/or increased dipping were also shown for evening than for awakening dosing of combinations; captopril/hydrochlorothiazide, enalapril/hydrochlorothiazide, trandolapril/verapamil valsartan/amlodipine, olmesartan/amlodipine, fosinopril/amlodipine, valsartan/hydrochlorothiazide, amlodipine/hydrochlorothiazide, amiloride/hydrochlorothiazide, telmisartan/amlodipine, losartan/indapamide, perindopril/indapamide, azilsartan/indapamide and valsartan/indapamide [25]. Furthermore, Hermida et al [26] performed a prospective endpoint trial with 19,084 hypertensive patients aged 60.5 ± 13.7 and demonstrated that bedtime hypertension treatment significantly reduces cardiovascular risk.…”

Section: Introductionmentioning

confidence: 92%

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: Introductionmentioning

confidence: 92%

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

2022

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Pioneering new frontiers in circadian medicine chronotherapies for cardiovascular health

Festus,

Spilberg,

Young

et al. 2024

Trends in Endocrinology & Metabolism

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Chronobiology and the Kidney

Knapp

2024

Chronobiology and Chronomedicine

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The kidney plays a critical role in maintaining a stable internal environment by balancing output and intake, circadian variations in the contents of intracellular and extracellular fluids, the levels of some pharmaceuticals and total body water volume. Variations in the quantities of daytime and night-time urine were recorded in early observations of humans and later studied in manipulated light/dark environments, in clinical disorders and in laboratory animals. Circadian variations in the transfer of substances from the gastrointestinal tract and in metabolism influence the volume and content of urine. The nephron tubules are responsible for transferring solutes and water, modifying glomerular filtrate as it transits through them. In both health and many disorders, changes are necessary to balance intake and output, and circadian variations result from the influence of clock genes. Exogenous changes from an erect to supine position, during sleep and due to extrinsic events may modify intrinsic circadian rhythms, as can illness. Renal transplantation can change day-to-night variability. The circadian timing of medication can modify renal responses. Benefits, toxicity and side effects may change with the timing of administration of medication. A “best” circadian timing for medications prescribed for renal conditions and times of administration that result in modified side effects are often found.

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Ingestion-time differences in the pharmacodynamics of dual-combination hypertension therapies: Systematic review and meta-analysis of published human trials

Cited by 6 publications

References 59 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

Pioneering new frontiers in circadian medicine chronotherapies for cardiovascular health

Chronobiology and the Kidney

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