Summary: Plasma digoxin concentrations were measured by radioimmunoassay in 116 patients with atrial fibrillation on long-term oral treatment with the drug, and in 23 patients with digoxin toxicity. The mean concentrations were 1-4 ng./ml. and 3.1 ng./ml., respectively. Though an overlap occurred between the therapeutic and toxic ranges, toxicity is unlikely to occur below a level of 2 ng./ml. Plasma concentration showed a poor correlation with resting heart rate during atrial fibrillation. In patients with good renal function, however, a significant correlation was found between oral dose and plasma concentration. No evidence was obtained for increased sensitivity to therapeutic concentrations of the drug in elderly subjects, but the doses required to achieve these concentrations tended to be less than in younger patients.

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Methods SummaryAfter the oral administration of 0-5 mg of digoxin in tablet form to fasting subjects peak plasma levels were reached in 30 to 60 minutes. Levels then fell to reach a plateau at six to eight hours. When the same dose was given after food the peak plasma concentrations were significantly lower, but the concentrations reached in samples obtained from two to eight hours after the dose did not differ appreciably from corresponding samples obtained in the fasting experiments.In a four-week cross-over study of 21 patients on maintenance therapy, digoxin taken regularly in the fasting state produced plasma concentrations similar to those obtained when the drug was taken after meals.The rapid appearance of digoxin in the blood suggests that the oral route of administration is adequate for most patients who require rapid digitalization, and the timing of maintenance dosage in relation to meals is unimportant.

Plasma digoxin concentrations were measured in II chronically digitalized patients during and after cardiac operation involving cardiopulmonary bypass. The mean concentration fell from I 5 ng/ml (i ng= IO-9 g) at induction of anaesthesia to I I ng/ml after 2 hours of bypass. This fall was due principally to dilution of the plasma volume by the oxygenator prime and by transfusion. The mean concentration on the first postoperative day was 1-7 ng/ml. Thus cardiopulmonary bypass does not cause any appreciable increase in digoxin excretion or loss. On the other hand, by temporarily impairing renal function and reducing the plasma concentrations of potassium and magnesium, it tends to reduce maintenance requirements of digoxin.The management of patients after cardiac operations is frequently hindered by uncertainty regarding the effect of cardiopulmonary bypass on the degree of digitalization. Heart rate in this situation is an unreliable guide even in the presence of atrial fibrillation, and clinicians may be in doubt whether arrhythmias should be treated by withholding or by increasing doses of digoxin. The information concerning the effect of cardiopulmonary bypass on plasma levels of digoxin available until now has depended upon experiments in which small doses of tritiated digoxin have been given to patients before operation. Beall et al. (I963) found that labelled digoxin could be detected in the pump oxygenator after patients had undergone a period of cardiopulmonary bypass, but that whereas small reductions in plasma concentration of digoxin occurred, no fall in myocardial concentration could be measured over the period of operation. Ebert, Morrow, and Austen (I963) conducted similar studies and reported reductions of up to 28 per cent in myocardial digoxin concentrations. However, the design of these experiments did not permit the accumulation of tissue stores of labelled digoxin, and the results may not be applicable to patients on long-term treatment with the drug.

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