Digitalis

Abstract

The intestinal absorption of digoxin is essentially a passive non-saturable diffusion process, although a saturable carrier-mediated component also plays an important role. The bioavailability varies between 40 and 100%: the presence of food may reduce the peak serum concentration, but does not reduce the amount of digoxin absorbed. Recent development of a capsule containing a hydroalcoholic vehicle may reduce interindividual variations in absorption. Pharmacokinetic analysis of the distribution of digoxin suggests 3 compartments, the slow distribution phase accounting for the lag time between the inotropic effects and the plasma concentration profile. Digoxin is extensively bound to tissues such as myocardium, renal, skeletal muscle as well as red blood cells, but not to adipose tissue. Plasma protein binding varies between 20 and 30%: displacement of digoxin from protein binding sites does not cause significant clinical effects. As expected, haemodialysis or exchange transfusions do not significantly alter the body load of digoxin. The apparent volume of distribution of digoxin varies between 5 and 7.3 L/kg; this may be reduced by, for example, electrolyte abnormalities which reduce digoxin binding to the myocardium. The elimination half-life of digoxin is 36 hours, with 60 to 80% being excreted unchanged, by passive glomerular filtration and active tubular secretion. The remainder is excreted non-renally. Clearance is therefore dependent on renal function and declines in renal disease and in elderly patients. Digoxin interacts with other drugs at any stage of absorption (e.g. cholestyramine), distribution (e.g. quinidine), metabolism (e.g. phenytoin) or elimination (e.g. diltiazem). Patients should, therefore, be carefully monitored when changing a therapeutic regimen which includes any drugs known to interact with digoxin. Clinical monitoring is more important than therapeutic drug monitoring which should be reserved for suspected toxicity, doubts about efficacy, or in cases of poor compliance. With the advent of newer treatment modalities, digoxin is no longer the treatment of first choice in supraventricular arrhythmias and congestive heart failure. However, with careful monitoring, digoxin remains an important therapeutic option.

Cystatin C vs creatinine as markers of renal function in patients on digoxin treatment

“…Digoxin has a half-life of approximately 1.5 days and the drug is mainly eliminated unchanged in the urine [12]. Glomerular filtration rate (GFR) has a major impact on s-digoxin [12].…”

“…Digoxin has a half-life of approximately 1.5 days and the drug is mainly eliminated unchanged in the urine [12]. Glomerular filtration rate (GFR) has a major impact on s-digoxin [12]. As geriatric patients often have reduced GFR, monitoring kidney function during digoxin treatment is important.…”

Machine Learning-Based Prediction of Digoxin Toxicity in Heart Failure: A Multicenter Retrospective Study

“…Digoxin treatment is likely to result in inter-individual plasma concentrations because of its large distribution volume (7.3 L/kg) and long half-life (24-36 h). 9) Because the urinary excretion rate of the unchanged form of digoxin is 60-80%, 9) renal dysfunction is a significant risk factor for its increased plasma concentrations. 10) HF often complicates renal injury because it disturbs systemic circulation and organ perfusion, especially in patients with HF.…”

Population pharmacokinetics and optimization of the dosing regimen of digoxin in adult patients

“…Digoxin is widely prescribed for the treatment of congestive heart failure and atrial fibrillation. Therapeutic drug monitoring of digoxin is recommended because of its narrow therapeutic range [ 1 , 2 ]. Previous studies have reported several equations and nomograms to enable physicians to determine the appropriate dosage of digoxin for individual patients [ 3 , 4 ].…”