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Electrophoresis May 2022Cardiac glycosides digoxin and digitoxin are used in therapy for the treatment of congestive heart failure. Moreover, these compounds can be responsible for intoxication...
Development of a new ultra-high-performance liquid chromatography-tandem mass spectrometry method for the determination of digoxin and digitoxin in plasma: Comparison with a clinical immunoassay.
Cardiac glycosides digoxin and digitoxin are used in therapy for the treatment of congestive heart failure. Moreover, these compounds can be responsible for intoxication cases caused by fortuitous ingestion of leaves of Digitalis. Due to the narrow therapeutic range of these drugs, therapeutic drug monitoring is recommended in the clinical practice. In this context, immunoassays-based methods are generally employed but digoxin- and digitoxin-like compounds can interfere with the analysis. The aim of this study was to develop and validate an original UPLC-MS/MS method for the determination of digoxin and digitoxin in plasma. The method shows adequate sensitivity and selectivity with acceptable matrix effects and very good linearity, accuracy, precision, and recovery. A simple liquid-liquid extraction procedure was used for sample clean-up. The method was applied for the analysis of n = 220 plasma samples collected in two different clinical chemistry laboratories and previously tested by the same immunoassay. The statistical comparison showed a relevant negative bias of the UPLC-MS/MS method versus the immunoassay. These results are consistent with an immunoassay overestimation of digoxin plasmatic levels due to cross-reaction events with endogenous digoxin-like substances.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Digitoxin; Digoxin; Immunoassay; Tandem Mass Spectrometry
PubMed: 35132652
DOI: 10.1002/elps.202100290 -
Journal of Clinical Laboratory Analysis 2006Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are sometimes used in conjunction with digoxin for patient management. Spironolactone,...
A new enzyme-linked chemiluminescent immunosorbent digoxin assay is virtually free from interference of spironolactone, potassium canrenoate, and their common metabolite canrenone.
Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are sometimes used in conjunction with digoxin for patient management. Spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with serum digoxin measurement using various immunoassays. Recently a new enzyme-linked chemiluminescent immunosorbent digoxin assay (ECLIA-Digoxin) became commercially available for application on the ADVIA IMS 800i modular system (Bayer HealthCare, Tarrytown, NY). We investigated the potential interference of spironolactone and related compounds in this assay by comparing the results with the fluorescence polarization immunoassay (FPIA), which is known to have significant cross-reactivity with these compounds as well as a turbidimetric assay for digoxin with no known cross-reactivity with spironolactone and related compounds. Aliquots of drug free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin concentrations were measured. No apparent digoxin concentration was observed using the ECLIA-Digoxin or turbidimetric assay. When serum pools prepared from patients receiving digoxin were further supplemented with these compounds, we observed no significant change in digoxin concentrations in the presence of these compounds with the ECLIA-Digoxin. We conclude that this assay is virtually free from interferences from spironolactone, potassium canrenoate and their common metabolite canrenone.
Topics: Artifacts; Canrenone; Cross Reactions; Digoxin; Enzyme-Linked Immunosorbent Assay; Fluorescence Polarization Immunoassay; Humans; Luminescent Measurements; Nephelometry and Turbidimetry; Reagent Kits, Diagnostic; Sensitivity and Specificity; Spironolactone
PubMed: 16960898
DOI: 10.1002/jcla.20133 -
Circulation. Heart Failure Jan 2014Recent data on digoxin prescribing and adverse events are lacking but could help inform the management of digoxin in contemporary heart failure treatment.
BACKGROUND
Recent data on digoxin prescribing and adverse events are lacking but could help inform the management of digoxin in contemporary heart failure treatment.
METHODS AND RESULTS
We determined nationally representative numbers and rates of emergency department (ED) visits for digoxin toxicity in the United States using 2005 to 2010 reports from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project and the National Ambulatory (and Hospital Ambulatory) Medical Care Surveys. Based on 441 cases, an estimated 5156 (95% confidence interval [CI], 2663-7648) ED visits for digoxin toxicity occurred annually in the United States; more than three fourths (78.8% [95% CI, 73.5%-84.1%]) resulted in hospitalization. Serum digoxin level was ≥2.0 ng/mL for 95.8% (95% CI, 93.2%-98.4%) of estimated ED visits with levels reported (n=251 cases). The rate of ED visits per 10 000 outpatient prescription visits among patients≥85 years was twice that of patients 40 to 84 years (rate ratio, 2.4 [95% CI, 1.2-5.0]); among women, the rate was twice that of men (rate ratio, 2.3 [95% CI, 1.1-4.7]). Digoxin toxicity accounted for an estimated 1.0% (95% CI, 0.6%-1.4%) of ED visits for all adverse drug events among patients≥40 years, but an estimated 3.3% (95% CI, 2.3%-4.4%) of ED visits and 5.9% (95% CI, 4.0%-7.9%) of hospitalizations for all adverse drug events among patients≥85 years. Estimated annual ED visits and hospitalizations remained relatively constant from 2005 to 2010.
CONCLUSIONS
Digoxin toxicity is not declining; more careful prescribing to high-risk groups and improved monitoring of serum levels might be needed to reduce morbidity from outpatient digoxin use.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Anti-Arrhythmia Agents; Digoxin; Disease Management; Emergency Service, Hospital; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Sex Factors; United States
PubMed: 24300242
DOI: 10.1161/CIRCHEARTFAILURE.113.000784 -
British Journal of Clinical Pharmacology May 19781 The influence of particle size on absorption of digoxin was studied in ten healthy volunteers who received 0.5 mg digoxin as two standard Lanoxin tablets, or tablets... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1 The influence of particle size on absorption of digoxin was studied in ten healthy volunteers who received 0.5 mg digoxin as two standard Lanoxin tablets, or tablets containing micronized digoxin or large particle size digoxin. Tablets were given 30 min after 15 mg propantheline, 10 mg metoclopramine or a placebo tablet, and following an overnight fast. 2 The overall mean cumulative 4 day urinary excretion of digoxin was significantly lower (P less than 0.01) after large particle size digoxin than after standard or micronized digoxin. Mean cumulative urinary excretion following large particle size digoxin was reduced when administered after metoclopramide and increased after propantheline, the difference between these two treatments being significant (P less than 0.05). There was a significantly lower (P less than 0.05) overall mean cumulative excretion following standard by comparison with micronized digoxin. However, by comparison with placebo, neither metoclopramide nor propantheline significantly altered mean cumulative excretion after standard or micronized digoxin. Propantheline and metoclopramide affect absorption of digoxin from formulations of large particle size and slow dissolution rate only.
Topics: Adult; Digoxin; Female; Humans; Intestinal Absorption; Male; Metoclopramide; Middle Aged; Particle Size; Placebos; Propantheline
PubMed: 656287
DOI: 10.1111/j.1365-2125.1978.tb01657.x -
Emergencias : Revista de La Sociedad... Feb 2019Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning. (Observational Study)
Observational Study
OBJECTIVES
Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning.
MATERIAL AND METHODS
Descriptive observational study of digoxin poisonings attended in the emergency departments of 4 hospitals in Catalonia from 2013 through 2015. We gathered data relevant to the poisonings and recorded immediate and 30-day mortality. Factors possibly related to mortality were explored.
RESULTS
A total of 171 digoxin poisonings were attended. Seven (4.1%) were acute and 164 (95.9%) were chronic. The immediate and 30-day mortality rates were 6.4% and 13.4%, respectively. Bivariate analysis did not identify factors related to immediate mortality. However, the variables more often associated with 30-day mortality in this analysis were acute poisoning (after which 13% died vs 2.7% of those with chronic poisoning, P=.05), suicide attempts (8.7% of whom died vs 0.7%, P=.048), more compromised renal function (21.7% vs 9.5%, P=.037), fewer neurologic symptoms (4.3% vs 17.8% with more symptoms, P=.005), higher mean digoxin concentrations (4.7 mg/dL in those who died vs 3.7 mg/dL, P=.027), and a lower Barthel index (mean [SD] 49.1 [33.4] in those who died vs 70.3 [28.5]; P=.006). Logistic regression analysis identified serum digoxin concentration to be independently associated with immediate mortality. A lower Barthel index was associated with 30-day mortality.
CONCLUSION
Immediate mortality is related to a high digoxin concentration in serum, and 30-day mortality to a low Barthel index.
Topics: Adult; Aged; Aged, 80 and over; Digoxin; Emergency Service, Hospital; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Poisoning; Spain
PubMed: 30656872
DOI: No ID Found -
British Journal of Pharmacology Jun 19781 Twenty-nine dogs were given digoxin (0.25 mg) by mouth twice daily for eight days. Some of them (group 1) also received diuretics and others (group 2) a... (Comparative Study)
Comparative Study
1 Twenty-nine dogs were given digoxin (0.25 mg) by mouth twice daily for eight days. Some of them (group 1) also received diuretics and others (group 2) a mineralocorticoid. The dogs were then given an intravenous bolus injection of digoxin and plasma and cardiac muscle were analysed for digoxin and potassium. 2 In the digitalized dogs, myocardial potassium concentration decreased following the intravenous injection of either 0.05 or 0.15 mg/kg digoxin; in contrast, in those dogs given diuretics or mineralocorticoid the potassium concentration increased. 3 Ventricular arrhythmias occurred after digoxin injection (0.05 mg/kg) in the hypokalemic dogs, in those given a mineralocortocoid and in those dogs which received a toxic digoxin dose (0.15 mg/kg). No arrhythmias where seen in the control (digitalized) group. 4 Myocardial digoxin concentrations were similar in the control digitalized group and in the mineralocorticoid-treated dogs after the intravenous administration of the lower digoxin dose (0.05 mg/kg). The myocardial digoxin concentration was significantly higher in the hypokalemic group and in the group receiving the higher digoxin dose (0.15 mg/kg). 5 There was no obvious relationship between the occurrence of arrhythmias and the myocardial concentration of digoxin or potassium.
Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Hemodynamics; Myocardium; Potassium; Sodium; Time Factors
PubMed: 667416
DOI: 10.1111/j.1476-5381.1978.tb09751.x -
Journal of Healthcare Engineering 2018Digoxin is a high-alert medication because of its narrow therapeutic range and high drug-to-drug interactions (DDIs). Approximately 50% of digoxin toxicity cases are...
Digoxin is a high-alert medication because of its narrow therapeutic range and high drug-to-drug interactions (DDIs). Approximately 50% of digoxin toxicity cases are preventable, which motivated us to improve the treatment outcomes of digoxin. The objective of this study is to apply machine learning techniques to predict the appropriateness of initial digoxin dosage. A total of 307 inpatients who had their conditions treated with digoxin between 2004 and 2013 at a medical center in Taiwan were collected in the study. Ten independent variables, including demographic information, laboratory data, and whether the patients had CHF were also noted. A patient with serum digoxin concentration being controlled at 0.5-0.9 ng/mL after his/her initial digoxin dosage was defined as having an appropriate use of digoxin; otherwise, a patient was defined as having an inappropriate use of digoxin. Weka 3.7.3, an open source machine learning software, was adopted to develop prediction models. Six machine learning techniques were considered, including decision tree (C4.5), -nearest neighbors (kNN), classification and regression tree (CART), randomForest (RF), multilayer perceptron (MLP), and logistic regression (LGR). In the non-DDI group, the area under ROC curve (AUC) of RF (0.912) was excellent, followed by that of MLP (0.813), CART (0.791), and C4.5 (0.784); the remaining classifiers performed poorly. For the DDI group, the AUC of RF (0.892) was the best, followed by CART (0.795), MLP (0.777), and C4.5 (0.774); the other classifiers' performances were less than ideal. The decision tree-based approaches and MLP exhibited markedly superior accuracy performance, regardless of DDI status. Although digoxin is a high-alert medication, its initial dose can be accurately determined by using data mining techniques such as decision tree-based and MLP approaches. Developing a dosage decision support system may serve as a supplementary tool for clinicians and also increase drug safety in clinical practice.
Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Decision Support Systems, Clinical; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Machine Learning; Male; Middle Aged; Young Adult
PubMed: 30210752
DOI: 10.1155/2018/3948245 -
Congestive Heart Failure (Greenwich,... 2005Gender differences in drug pharmacokinetics and pharmacodynamics have been recognized for some time. This issue has generally been ignored in clinical practice, despite... (Review)
Review
Gender differences in drug pharmacokinetics and pharmacodynamics have been recognized for some time. This issue has generally been ignored in clinical practice, despite there being ample evidence to suggest that gender can influence multiple aspects of pharmacokinetics. Gastric acid secretion, gastrointestinal blood flow, proportions of muscular and adipose tissue, the amount of drug-binding proteins, gender-specific changes in the available amount of P450 isozymes, physiologic and hormonal changes during the menstrual cycle, and differences in renal blood flow are several factors that may have some bearing on sex-related differences in pharmacokinetics. Furthermore, female-specific issues such as pregnancy, menopause, oral contraceptive use, and menstruation may independently influence drug metabolism and serve as confounders to the interpretation of gender differences in drug handling or effect. While gender-related pharmacodynamic data are limited, evidence suggests that women are more prone to the development of torsade de pointes from proarrhythmic drugs such as quinidine or d-sotalol and have an increased cardiovascular risk with the use of digoxin. The specific risk:benefit ratio for individual cardiovascular medications should be more routinely considered in the context of gender.
Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors; Women's Health
PubMed: 15947543
DOI: 10.1111/j.1527-5299.2005.04171.x -
Anais Da Academia Brasileira de Ciencias 2015Digoxin is used for heart failure associated to systolic dysfunction and high ventricular rate. It has a narrow therapeutic range and intoxication may occur due to drug...
Digoxin is used for heart failure associated to systolic dysfunction and high ventricular rate. It has a narrow therapeutic range and intoxication may occur due to drug interactions or comorbidities. The aim of this work was to study digoxin use in a public health unit delineating the profile of patients susceptible to digitalis intoxication. Medical records belonging to patients admitted to the cardiomyopathy ward of the health unit (2009-2010) and in use of digoxin were analyzed. Among 647 patients admitted, 185 individuals using digoxin and possessed records available. The registration of plasma digoxin concentration was found in 80 records and it was out of the therapeutic range in 42 patients (52.5%). This group of individuals was constituted mainly by males patients (79%), functional class III of heart failure (65%), exhibiting renal failure (33%). The evaluated sample reflects the epidemiology of heart failure in Brazil and, although pharmacotherapy had been according to Brazilian Guidelines, apparently the monitoring was not performed as recommended. This work highlighs the necessity of plasma digoxin constant monitoring during pharmacotherapy and the development of protocols that enable a safer use, especially in male patients, functional class III and with renal dysfunction.
Topics: Adult; Brazil; Cardiotonic Agents; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Public Health; Retrospective Studies; Severity of Illness Index; Young Adult
PubMed: 25993358
DOI: 10.1590/0001-3765201520140133 -
American Heart Journal Aug 1974
Comparative Study Review
Topics: Administration, Oral; Animals; Biopharmaceutics; Cats; Digoxin; Guinea Pigs; Half-Life; Heart Diseases; Humans; Kidney; Kidney Diseases; Kinetics; Models, Theoretical; Protein Binding; Radioimmunoassay; Serum Albumin; Solutions; Tablets; Tritium; United Kingdom; United States
PubMed: 4601506
DOI: 10.1016/0002-8703(74)90001-5