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The Journal of Clinical Investigation Feb 1977Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H] digoxin-treated dogs. Both...
Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H] digoxin-treated dogs. Both classes of molecule remove digoxin from the extravascular space and sequester it in the circulation in protein-bound form, a form in which the digoxin is presumably inactive. These two classes of molecule differ, however, in that the intact antibody molecules interfere with digoxin excretion, thereby promoting the retention of the glycoside; this retained digoxin is eventually released in free, active form when the administered antibody is metabolically degraded. In contrast, urinary excretion of digoxin continues in Fab-treated dogs, with significant quantities of digoxin being excreted promptly in the urine in complex with Fab fragments. These differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibody Specificity; Digoxin; Dogs; Female; Immunoglobulin Fab Fragments; Serum Sickness; Sheep
PubMed: 299860
DOI: 10.1172/JCI108647 -
Journal of Cardiac Failure Apr 2022
Do the Favorable Effects of Digoxin and SGLT2 Inhibitors Really Differ in Patients with Heart Failure and a Reduced Ejection Fraction? A Provocative Side-by-Side Examination of Trial Outcomes.
Topics: Diabetes Mellitus, Type 2; Digoxin; Glucosides; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 35038597
DOI: 10.1016/j.cardfail.2022.01.001 -
British Heart Journal Jun 1989A randomised, double blind, placebo controlled, crossover study of digoxin withdrawal and reintroduction was carried out over two periods of eight weeks each after long... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A randomised, double blind, placebo controlled, crossover study of digoxin withdrawal and reintroduction was carried out over two periods of eight weeks each after long term treatment. Forty four patients with stable heart failure in sinus rhythm and plasma digoxin concentrations over 0.8 ng/ml were studied. Their progress was assessed by clinical criteria, by haemodynamic measurements (systolic time intervals and echocardiography), and by pharmacological measurements of erythrocytic sodium pump numbers and activity. After withdrawal of digoxin clinical deterioration occurred in only 25% of the patients. Furthermore, in only 9% of cases was digoxin reintroduction thought to be necessary. There was deterioration in only 11% of the patients during digoxin treatment. Deterioration during digoxin withdrawal was accompanied by changes in systolic time intervals, but similar, albeit smaller changes in systolic time intervals also occurred in patients with no deterioration. Deterioration was accompanied by changes in the pharmacological effects of digoxin on the erythrocytes, consistent with a loss of effect, and these changes did not occur in those who did not deteriorate. The occurrence of deterioration could not be predicted by any clinical, haemodynamic, or pharmacological measurements made before withdrawal.
Topics: Adult; Aged; Cardiac Output, Low; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Administration Schedule; Female; Hemodynamics; Humans; Long-Term Care; Male; Middle Aged; Random Allocation; Systole
PubMed: 2503017
DOI: 10.1136/hrt.61.6.529 -
Bioscience Reports Jan 2016Drug-drug interactions (DDIs) and associated toxicity from cardiovascular drugs represents a major problem for effective co-administration of cardiovascular...
Drug-drug interactions (DDIs) and associated toxicity from cardiovascular drugs represents a major problem for effective co-administration of cardiovascular therapeutics. A significant amount of drug toxicity from DDIs occurs because of drug interactions and multiple cardiovascular drug binding to the efflux transporter P-glycoprotein (Pgp), which is particularly problematic for cardiovascular drugs because of their relatively low therapeutic indexes. The calcium channel antagonist, verapamil and the cardiac glycoside, digoxin, exhibit DDIs with Pgp through non-competitive inhibition of digoxin transport, which leads to elevated digoxin plasma concentrations and digoxin toxicity. In the present study, verapamil-induced ATPase activation kinetics were biphasic implying at least two verapamil-binding sites on Pgp, whereas monophasic digoxin activation of Pgp-coupled ATPase kinetics suggested a single digoxin-binding site. Using intrinsic protein fluorescence and the saturation transfer double difference (STDD) NMR techniques to probe drug-Pgp interactions, verapamil was found to have little effect on digoxin-Pgp interactions at low concentrations of verapamil, which is consistent with simultaneous binding of the drugs and non-competitive inhibition. Higher concentrations of verapamil caused significant disruption of digoxin-Pgp interactions that suggested overlapping and competing drug-binding sites. These interactions correlated to drug-induced conformational changes deduced from acrylamide quenching of Pgp tryptophan fluorescence. Also, Pgp-coupled ATPase activity kinetics measured with a range of verapamil and digoxin concentrations fit well to a DDI model encompassing non-competitive and competitive inhibition of digoxin by verapamil. The results and previous transport studies were combined into a comprehensive model of verapamil-digoxin DDIs encompassing drug binding, ATP hydrolysis, transport and conformational changes.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Animals; Biological Transport, Active; Digoxin; Drug Interactions; Mice; Models, Chemical; Verapamil
PubMed: 26823559
DOI: 10.1042/BSR20150317 -
Clinical Cardiology Feb 1979Following the development of digoxin radioimmunoassay, we noted that serum digoxin concentrations appeared to rise in patients given quinidine. To further evaluate this...
Following the development of digoxin radioimmunoassay, we noted that serum digoxin concentrations appeared to rise in patients given quinidine. To further evaluate this important possible interaction between digoxin and quinidine, charts from 863 cardiology patients were reviewed. Ninety two patients received both drugs after having been on digoxin alone; 38 were ineligible for the study because of insufficient data and 27 were excluded because of changing renal function and/or concomitant antiarrhythmic drug therapy, leaving 27. Serum digoxin increased in 25 of the 27 study patients (93%) during quinidine therapy; mean serum digoxin rose from 1.4 ng/ml before quinidine to 3.2 ng/ml during quinidine. Anorexia, nausea and/or vomiting developed in 16 patients (59%) during quinidine therapy, but disappeared in all 10 patients in whom digoxin alone was reduced in dose, suggesting that digoxin had a causative role in the appearance of these symptoms although they developed only after quinidine had begun. Three of thirteen patients with only atrial arrhythmias on digoxin prior to quinidine developed new ventricular premature depolarizations (VPD) after starting quinidine; two of these three as well as four patients with prior VPDs developed new ventricular tachycardia, ventricular fibrillation, asystole, or sudden death. When starting quinidine in patients who are taking digoxin, the clinical course, ECG and serum digoxin should be followed closely.
Topics: Adult; Aged; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Middle Aged; Quinidine; Retrospective Studies
PubMed: 498605
DOI: 10.1002/clc.4960020107 -
British Medical Journal (Clinical... Jun 1983
Topics: Digitalis Glycosides; Digoxin; Humans
PubMed: 6407665
DOI: 10.1136/bmj.286.6382.1975-e -
British Medical Journal May 1977
Topics: Arrhythmias, Cardiac; Digoxin; Drug Administration Schedule; Humans
PubMed: 861621
DOI: 10.1136/bmj.1.6072.1350-d -
British Medical Journal May 1972
Topics: Aged; Digoxin; Humans; Tablets
PubMed: 5023918
DOI: 10.1136/bmj.2.5810.403-a -
British Medical Journal Sep 1972
Topics: Biopharmaceutics; Digoxin; Dosage Forms; Humans; Intestinal Absorption; Pharmaceutical Preparations; Therapeutic Equivalency
PubMed: 5071688
DOI: No ID Found -
Proceedings of the National Academy of... Jan 1967
Topics: Animals; Antibody Formation; Cortisone; Dehydroepiandrosterone; Dialysis; Digoxin; Hydrocortisone; Rabbits; Serum Albumin, Bovine; Tritium
PubMed: 4227743
DOI: 10.1073/pnas.57.1.71