Current concepts of digoxin therapy.
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Biomedical subjects
Publications and source records attributed to F I Marcus.
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The pharmacokinetics of the cardiac glycofides have been elucidated as a result of the development of assays of sufficient sensitivity to measure the concentration of digitalis compounds in biological fluids. Digoxin can accumulate in the body without the administration of a loading dose, and a steady state blood concentration will be reached in 5 to 7 days. Digitoxin requires 35 days to accumulate to a plateau. If a loading dose of digoxin is used, it should be approximately three times the estimated daily maintenance dose. Factors that determine the selection of the appropriate maintenance dose of digoxin include renal function and lean body mass. Digitoxin is less dependent on renal function for its elimination than is digoxin. Knowledge of the pharmacokinetics of digitalis preparations is useful in determining how to change from one cardiac glycoside to another, each with different half-lives. One should wait 3 days before starting digoxin therapy when changing from maintenance digitoxin to digoxin (assuming normal renal function). The pharmacokinetics of changing from ouabain to digoxin without loss of digitalis effect are described. The metabolism of the commonly used digitalis preparations are summarized.
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Derivatives of digoxin and digitoxin were measured by the Na-K-ATPase displacement assay and by radioimmunoassay and the data compared with biological potency of these compounds. There was a slightly higher affinity of digoxigenin-bis-digitoxoside as compared with digoxin using digoxin-specific antiserum and considerably less affinity of digoxigenin and dihydrodigoxin than the parent compound in the same system. A similar trend was observed for the derivatives of digitoxin using digoxin-specific antiserum. The recovery on extraction of some of the derivatives of digoxin and digitoxin differed from that of the parent compounds in the ATPase assay. The potency of the derivatives of these drugs in displacing 3H ouabain also differed from the parent compoundmboth the recovery on extraction and the potency for displacing ouabain must be considered in the estimation of the contribution of the derivatives of digoxin or digitoxin to the result of Na-K-ATPase assay. Quantitative information of the metabolites of digoxin and digitoxin in normal and pathological conditions is needed to properly interpret assay data obtained either by radioimmunoassay or by ATPase assay.
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