Digoxin kinetics in patients with thyroid dysfunction.

Abstract

The disposition of intravenously administered (3H)‐digoxin has been studied in 9 hyperthyroid and 4 hypothyroid patients. In 9 of these subjects the handling of simultaneously administered oral digoxin was assessed from serum digoxin levels determined by radioimmunoassay. Glomerular filtration rate was measured in each individual at the end of the period of study. There was a close correlation (p < 0.001) between digoxin renal clearance and glomerular filtration rate. Considerable overlap was observed when estimates of digoxin renal clearance in hyperthyroid persons were compared with those obtained in normal control subjects and hypothyroid patients, and there was no correlation between the severity of thyrotoxicosis and digoxin renal clearance; in fact, 3 thyrotoxic patients with established or paroxysmal atrial fibrillation showed impaired digoxin renal clearance. No consistent abnormality of digoxin extrarenal clearance was observed in this group of patients with thyroid disease and digoxin absorption was normal in 9 subjects in whom measurement of this parameter was possible (percent absorption, 71 ± 15). Analysis of the ratio of digoxin concentration in the “deep” compartment to digoxin concentration in the “central” compartment was made by means of a three‐compartment open kinetic model; this revealed a significantly greater “tissue” concentration of digoxin in thyrotoxic patients when compared with hypothyroid patients. These results suggest that the well‐recognized insensitivity of thyrotoxic patients to cardiac glycosides is inexplicable on pharmacokinetic grounds.