The administration of quinidine to patients receiving digoxin maintenance therapy results in a marked increase in the serum/plasma digoxin concentration. With over 90% of patients being affected the incidence of this drug interaction is rather high. The change in serum digoxin concentration is proportional to the dose of quinidine. At usual therapeutic doses of quinidine, the serum digoxin concentration tends to double on the average, although there is pronounced individual variation, the reported increase ranging from 25 to over 300%. The serum digoxin concentration begins to rise within 24 hours after starting quinidine and a new steady-state level is established in about 3 to 6 days. It remains elevated for as long as quinidine is co-administered. Quinidine increases the serum digoxin concentration in anuric patients also; in these patients it may take a week or more until a new steady-state is established.The sustained elevation of serum digoxin concentration during quinidine co-administration is undoubtedly due to a decrease in total body clearance of digoxin. Quinidine decreases both renal and extrarenal clearance of digoxin. Obviously quinidine inter/eres with renal tubular excretion of digoxin since it affects neither the glomerular filtration rate nor protein binding of digoxin. The mechanism by which quinidine decreases extrarenal clearance of digoxin remains to be elucidated.Conflicting results have been reported with regard to the influence of quinidine on the elimination half-life (t'l,) and volume of distribution of digoxin. At least in the relevant patient group, i.e. in cardiac patients on long term treatment with combined digoxin and quinidine, the digoxin t", is apparently increased, but both no change and a substantial decrease in volume of distribution during q~inidine ,co-administration has been reported. Direct measurements of digoxin tissue levels in vivo seem to favour the latter finding. However, specific binding of digoxin in vitro is unaffected by quinidine at concentrations thought to be in the therapeutic range. Whether quinidine interferes with nonspecific binding of digoxin remains to be determined.The clinical effect on the heart of the increased serum digoxin concentration in the quinidine-digoxin interaction is still controversial. However, the evidence available at present strongly suggests that the increase results at least partially in an increased cardiac effect. Likewise, data provided recently by the Boston Drug Surveillance Program and several case reports indicate an increased digoxin toxicity during quinidine administration. Based on our present knowledge of this drug interaction, only tentative therapeutic recommendations can be given.
