The eJJects of diseases involving the kidney, gastrointestinal tract, thyroid, and cardiovascular system on the disposition of cardiac glycosides are reviewed.The glycosides ouabain and digoxin are cleared predominantly by renal excretion of the intact drugs. Not surprisingly, total clearance (if these two compounds is reduced in patients with reduced creatinine clearance. Similarly, steady-state serum concentrations of digoxin at any given dose become higher as renal function declines. However, individual variability is considerable, thereby limiting the utility (if dosage schemes based on nomograms or equations. A further complication is Ihal tissue distribution (if digoxin is altered in renal inSI!fficiency, so that serum concentrations take on u different meaning in patients with renal failure. In the ca.~e (if digitoxin, renal clearance accounts for only part of the total clearance. A clear relationship between creatinine clearance and total digitoxin clearance has not yet been established. However, digitoxin protein binding is reduced in renal insufficiency, requiring a change in the clinical interpretation (if total (free plus bound) digitoxin serum concentrations in such patients.
Although digoxin absorption may be impaired in patients with serious malabsorption syndromes, most studies have demonstrated normal or near normal absorption despite gastrointestinal disease or extensive ablative surgery. Hepatic cirrhosis does not alter the pharmacokinetics of digoxin, but is associated with impaired demethylation of ~-methyldigoxin (medigoxin). Although hepatic biotran~formation accounts for a substantialfraction (if the total clearance of digitoxin, disappearance (if digitoxin from the plasma is, if anything, more rapid in patients with liver disease as opposed to healthy controls.Clearance (if both digitoxin and digoxin varies in direct relation to thyroid function; clearance is increased and the ha(f-l!fe shortened in thyrotoxicosis, and the reverse is truefor hypothyroidism. This may be explained by parallel changes in creatinine clearance, but further studies are needed to d~fine the mechanism (if alterations in glycoside clearance in relation to thyroid function.Continuing re.finement of analytical and pharmacokinetic techniques will lead to rapid progress in research in this area, and a need for continuing re-evaluation of the state of the art.