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      Farmacocinética poblacional de la digoxina en pacientes de edad avanzada: una revisión sistemática Translated title: Population pharmacokinetics of digoxin in elderly patients: a systematic review

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          Abstract

          Resumen Objetivo: Resumir la literatura disponible sobre los estudios de farmacocinética poblacional de digoxina en pacientes de edad avanzada e identificar los cambios fisiopatológicos en esta subpoblación, que conllevan implicaciones clínicas en la farmacocinética de la digoxina. Método: Se realizó una revisión sistemática de los estudios de farmacocinética poblacional en pacientes ancianos que recibían digoxina. Se utilizaron PubMed, ISI Web of Science, SCOPUS y Science Direct para identificar los artículos con los descriptores (“Digoxin”[Mesh]) AND (“Pharmacokinetics”[Mesh]) AND (“Aged”[Mesh] OR “Elderly”[Mesh]), seguido de una búsqueda manual. Resultados: Se encontraron y revisaron nueve estudios, cinco de los cuales de desarrollaron en pacientes asiáticos. Se utilizó NONMEM para el análisis farmacocinético de los niveles plasmáticos de la digoxina, mayoritariamente descrita como un modelo monocompartimental. Conclusiones: Los pacientes ancianos presentan cambios fisiopatológicos con gran influencia en la farmacocinética de muchos fármacos. Las covariables con un mayor impacto en la farmacocinética de la digoxina deben tenerse en cuenta al ajustar la dosis de este medicamento en pacientes de edad avanzada con el fin de lograr beneficios óptimos para la salud y prevenir posibles efectos adversos en esta subpoblación.

          Translated abstract

          Abstract Objective: To resume the available literature about digoxin population pharmacokinetic studies in elderly patients. To identify the pathophysiological changes in this subpopulation with clinical implications on digoxin pharmacokinetics. Method: A systematic review was performed regarding the population pharmacokinetic studies in elderly patients receiving digoxin. PubMed, ISI Web of Science, SCOPUS and Science Direct were used to identify the articles with the descriptors (“Digoxin”[Mesh]) AND (“Pharmacokinetics”[Mesh]) AND (“Aged”[Mesh] OR “Elderly”[Mesh]), followed by a manual search. Results: Nine studies were found and reviewed, five of them carried out in Asian patients. NONMEM was used for pharmacokinetic analysis of digoxin blood levels, being mostly described by a one-compartment model. Serum creatinine, body weight and concomitant administration of calcium channel blockers are the covariates that most frequently influence digoxin pharmacokinetics in elderly patients. Conclusions: Elderly people present pathophysiological changes with influence on the pharmacokinetics of many drugs. The covariates with most influence on digoxin pharmacokinetics should be considered when adjusting this drug dosage in elder patients to achieve optimum health benefits and prevent possible side effects.

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          Most cited references62

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          Structural and Functional Changes With the Aging Kidney.

          Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.
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            Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications.

            Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
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              Aging biology and geriatric clinical pharmacology.

              Population aging evokes doomsday economic and sociological prognostication, despite a minority of older people suffering significant dependency and the potential for advances in therapeutics of age-related disease and primary aging. Biological aging processes are linked mechanistically to altered drug handling, altered physiological reserve, and pharmacodynamic responses. Parenteral loading doses need only be adjusted for body weight as volumes of distribution are little changed, whereas oral loading doses in some cases may require reduction to account for age-related increases in bioavailability. Age-related reduction of hepatic blood flow and hepatocyte mass and primary aging changes in hepatic sinusoidal endothelium with effects on drug transfer and oxygen delivery reduce hepatic drug clearance. Primary renal aging is evident, although renal clearance reduction in older people is predominantly disease-related and is poorly estimated by standard methods. The geriatric dosing axiom, "start low and go slow" is based on pharmacokinetic considerations and concern for adverse drug reactions, not from clinical trial data. In the absence of generalizable dosage guidelines, individualization via effect titration is required. Altered pharmacodynamics are well documented in the cardiovascular system, with changes in the autonomic system, autacoid receptors, drug receptors, and endothelial function to modify baseline cardiovascular tone and responses to stimuli such as postural change and feeding. Adverse drug reactions and polypharmacy represent major linkages to avoidable morbidity and mortality. This, combined with a deficient therapeutic evidence base, suggests that extrapolation of risk-benefit ratios from younger adults to geriatric populations is not necessarily valid. Even so, therapeutic advances generally may convert healthy longevity from an asset of fortunate individuals into a general social benefit.
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                Author and article information

                Journal
                fh
                Farmacia Hospitalaria
                Farm Hosp.
                Grupo Aula Médica (Toledo, Toledo, Spain )
                1130-6343
                2171-8695
                December 2022
                : 46
                : 6
                : 359-366
                Affiliations
                [2] Madrid Madrid orgnameUniversidad Complutense de Madrid orgdiv1Facultad de Farmacia orgdiv2Departamento de Farmacia Galénica y Tecnología Alimentaria Spain
                [1] Leganés Madrid orgnameHospital Universitario Severo Ochoa orgdiv1Servicio de Farmacia España
                Article
                S1130-63432022000600008 S1130-6343(22)04600600008
                10.7399/fh.13288
                7d90ff24-2c34-40bc-b526-d0558fb0a0c8

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 10 October 2022
                : 25 May 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 63, Pages: 8
                Product

                SciELO Spain

                Categories
                Revisiones

                Farmacocinética poblacional,Digoxina,Ancianos,Revisión,Population pharmacokinetics,Digoxin,Elderly,Systematic review

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