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Clinical Pharmacokinetics of Digoxin

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Summary

About 70 to 80% of an oral dose of digoxin is absorbed, mainly in the proximal part of the small intestine. The degree of binding to serum albumin is 20 to 30%. Digoxin is extensively distributed in the tissues, as reflected by the large volume of distribution. High concentrations are found in the heart and kidneys, but the skeletal muscles form the largest digoxin storage. The half-life of elimination in healthy persons varies between 26 and 45 hours.

The main route of elimination is renal excretion of digoxin, which is closely correlated with the glomerular filtration rate. In addition, some tubular secretion and perhaps tubular reabsorption occurs. Nearly all of the digoxin in the urine is excreted unchanged, with a small part as active metabolites. The clinical significance of dihydrodigoxin as a metabolite remains to be resolved. About 25 to 28% of digoxin is eliminated by nonrenal routes. Biliary excretion may rise up to 30% of a given dose, but the enterohepatic cycle seems to be of minor importance.

The pharmacodynamic effects of digoxin, including toxic symptoms, are correlated with the uptake of digoxin in the heart after a single dose and with the steady state serum digoxin concentration during maintenance therapy.

Impaired kidney function is the most important condition with an influence on the pharmacokinetics of digoxin. In addition to the renal clearance of creatinine, the bioavailability of the digoxin formulation used, the volume of distribution, the amount of extrarenal clearance, body weight and serum albumin concentration, are other factors which may modify the serum level of digoxin. Certain drug interactions may also occur during the absorptive phase. Exact prediction of serum digoxin concentrations by various dosage calculations has not succeeded. Since many factors may influence the sensitivity of the myocardium to digoxin, measurement of serum digoxin levels is only one, but a useful criterion, when making clinical decisions about adjustment of digoxin dosage.

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Authors and Affiliations

  1. Institute of Biomedicine, Department of Pharmacology, Turku University, 20520, Turku 52 SF, Finland

    Esko Iisalo

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  1. Esko Iisalo
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Iisalo, E. Clinical Pharmacokinetics of Digoxin. Clin Pharmacokinet 2, 1–16 (1977). https://doi.org/10.2165/00003088-197702010-00001

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  • DOI: https://doi.org/10.2165/00003088-197702010-00001

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