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Digitalis

An Update of Clinical Pharmacokinetics, Therapeutic Monitoring Techniques and Treatment Recommendations

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Summary

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.

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  1. Geriatric Research, Education and Clinical Center, Sepulveda Veterans Administration Medical Center, and The Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA

    Arshag D. Mooradian

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Mooradian, A.D. Digitalis. Clin-Pharmacokinet 15, 165–179 (1988). https://doi.org/10.2165/00003088-198815030-00002

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