Distribution of digoxin, digitoxin and their cardioactive metabolites in human heart and kidney

There are still few data available about the quantitative distribution of the cardioactive metabolites of digitalis glycosides in human tissues. We therefore developed a method for the specific determination of digoxin, digitoxin, their semi-synthetic derivatives and dependent cardioactive metabolites in autopsy samples of heart and kidney. Tissue extraction and purification steps were followed by HPLC separation and RIA quantitation. A collective of 6 patients on long-term treatment with therapeutic doses of ß-acetyldigoxin had a mean myocardial digoxin content of 46.1 ± 25.0 ng/g (SD); kidney: 50.3 ± 30.3 ng/g. Digoxigenin bisdigitoxoside represented the second most important metabolite with 11.0 ± 5.1 ng/g in the heart and 13.6 ± 3.5 ng/g in the kidney. Digoxigenin monodigitoxoside and digoxigenin followed respectively with mean tissue contents below 5 ng/g. In a collective of 7 patients on maintenance treatment with digitoxin the mean tissue levels were higher but the metabolic pattern was similar. We measured an average myocardial digitoxin content of 78.9 ± 38.4 ng/g and a renal content of 104.1 ± 44.1 ng/g. Digitoxigenin bisdigitoxoside was determined to be 15.4 ± 6.5 ng/g and 11.9 ± 1.5 ng/g respectively. The amount of digoxin formed by hydroxylation under long-term treatment with digitoxin in heart and kidney were approximately 10 ng/g. In three cases of digoxin intoxication the myocardial digoxin content was at least 1.3 fold, the kidney level at least 2.9 fold higher than the maximum therapeutic level. The contents of digoxigenin bisdigitoxoside in the kidney also ranged high. The quotient digoxin/digoxigenin bisdigitoxoside in the myocardium may be a further parameter for the differentiation between chronic and acute digoxin ingestion (2.8:1–4.3:1 in the therapeutic group on long term treatment, 9.8:1–10.1:1 in the cases of acute intoxication).