electrical cardioversion without a suitable period of withdrawal of digoxin (Gilbert and Cuddy, 1965). It seems likely that many patients with atrial fibrillation have latent digoxin toxicity which can readily become manifest without any increase in plasma concentration of the drug.In view of the wide variations in dose requirements needed to achieve control of the heart rate in atrial fibrillation, and the fact that many patients with atrial fibrillation may have slow heart rates with or without digoxin, the poor correlation between ventricular rate and plasma levels was to be expected. The extent to which plasma levels reflect myocardial concentrations in chronically digitalized patients, however, remains to be defined.
Daily Dose and Plasma LevelsThe relationship between the size of the daily dose and the plasma levels of digoxin was investigated. Because most of the drug is excreted unchanged by the kidneys (Marcus et al., 1964), renal function is as important as dose in determining blood levels. We therefore restricted the analysis to those patients who had normal or near-normal renal function indicated by blood urea concentrations of less than 40 mg./100 ml. The data presented in Fig. 3 show a significant relationship between oral dose and plasma levels. Several factors must have militated against more uniform blood levels. The patients were of different heights and weights; blood urea provides only a rough index of glomerular filtration rate; the potency of some commercially available digoxin tablets may vary widely (Feinberg, 1969); and blood samples were taken at intervals after the previous dose ranging from about 8 to 24 hours. Clearly, however, 0.5 mg. of digoxin daily will usually provide plasma levels in a satisfactory therapeutic range of 1 to 2 ng./ml. in the presence of normal renal function. Larger doses, or moderate doses in the presence of considerably impaired renal function, are associated with levels which fall within the toxic range.Di,oxin toxicity is particularly common in the elderlv (Soffer, 1961), and the suggestion has been made that this may be due in part to increased sensitivity to the drug (Feibush, 1959). We found, however, that blood levels in patients aged 60 and over with controlled atrial fibrillation were closely similar to the levels in younger patients (Fig. 4). The blood levels in the older age group were attained with a smaller mean dose, and the blood urea of these patients tended to be higher than those found in the under-60 group. This observation is consistent with the findings of Ewy, Kapadia, Yao, Lullin, and Marcus (1969), who used tritiated digoxin to show that a given dose of the drug resulted in higher blood concentrations in the elderly compared with younger subjects, and that the difference was associated with smaller body size and diminished urinary excretion of digoxin.The present findings indicate that the ventricular response to atrial fibrillation is not well correlated with plasma concentration of digoxin. Patients receiving more than 0.5 mg. daily o...
