Studies on digitalis. VI. The effect of heparin on serum protein binding of digitoxin and digoxin

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Abstract
The aim of the present study was to investigate the nature of the previously reported changes in the serum protein binding of digitoxin and digoxin in uremic patients under treatment with hemodialysis. Kinetic studies on protein binding during hemodialysis showed that the free fraction of digitoxin rose from 2.6% to 6.9% after 5 min of hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from 78.3% to 87.1 % during the same period. In vitro hemodialysis experiments showed that such changes occurred only in vivo. Injection of heparin (5,000 IU) to control subjects produced similar kinetic changes in the protein binding of digitoxin and digoxin. Free fatty acids changed in the same way. These results indicate that the heparin-induced release of free fatty acids causes displacement of digitoxin and digoxin from their albumin-binding sites. Patients on hemodialysis have lower serum levels of digitoxin and cardioactive metabolites (mean, 8.9 ng/ml) than control patients (mean, 16.7 ng/ml) (p < 0.005) on similar doses (mean, 0.085 mg/day). They should be maintained on the same digitoxin doses as uremic and control patients, but serum digitoxin levels should be adjusted to 10 to 15 ng/ml in hemodialysis patients compared to 15 to 25 ng/ml in uremic patients and in patients with normal renal function.