The Significance of the Enterohepatic Circulation on the Metabolism of Digoxin in Patients with the Ability of Intestinal Conversion of the Drug

Abstract

A cardiac patient had to be given a very high dosage of digoxin to attain therapeutic plasma level. The increased dosage requirement could partly be explained by reduced bioavailability due to intestinal conversion of digoxin. Consequently, the kinetics of the drug was examined before and after erythromycin treatment. Before treatment the determination of the area under the concentration versus time curve (AUC) following a single dose of digoxin given orally or intravenously demonstrated a substantial reduction in the absolute bioavailability. Erythromycin administration during 20 days caused a dramatic rise in AUC when the single oral dose was repeated, exceeding the two AUC obtained prior to initiation of the antibiotic therapy, and the steady state plasma digoxin level was 2-3-fold increased. The fact that the AUC obtained for a single oral dose of digoxin after erythromycin treatment exceeded that obtained when given intravenously before erythromycin indicated the presence of an enterohepatic circulation of digoxin. This may contribute substantially to the elimination of digoxin in patients with the capability of intestinal conversion of digoxin.