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It is well recognized that the co-administration of some drugs to persons receiving digoxin results in an increase of serum digoxin levels: it occasionally precipitates digoxin toxicity. There are some possible mechanisms by which different drugs may increase serum glycoside levels: 1) by displacing digoxin from tissue binding sites, 2) by decreasing digoxin renal excretion, 3) by enhancing digoxin absorption, 4) by increasing the inhibition of the ATP-dependent pump. Combined administration of calcium antagonists and B-methyldigoxin is common in patients with heart diseases. Other Authors have found that the co-administration of these drugs with digoxin increases glycoside serum levels, without signs of intoxication. We have examined the effects of this combination on digitalis activity, by Rubidium 86 uptake in erythrocytes. Thirty patients aged 52 to 66 with congestive heart failure were studied. All of these had normal serum creatinine, blood urea and serum protein levels. These subjects received 0,20 mg of B-methyldigoxin daily for nine days; afterwards, ten of them were given in addition 320 mg of verapamil for seven days; the other ten received in addition 60 mg of nifedipine, for seven days; the remaining ten patients received in addition 320 mg of verapamil and 60 mg of nifedipine together, for seven days. Digoxin activity was measured on the eighth, ninth and sixteenth day of treatment by Rubidium 86 uptake in erythrocytes. The technique was that of Bertler. Means were compared with the t test, with the assumption of the equal variances in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Digoxin and Verapamil may often be used in association in heart diseases; we tested whether this coadministration increases digitalis activity. Ten patients with failing heart were given 0.10 mg of beta-methyldigoxin, twice a day, for nine days; then they received in addition 80 mg of Verapamil, four times a day, for seven days. Digoxin activity was measured on the eighth, ninth and 16th days of treatment by 86Rubidium uptake in erythrocytes. The steady-state concentration was 0.91 +/- 0.13 ng/ml; during the coadministration the concentration rose to 1.23 +/- 0.16 ng/ml (an increase of 35.12%). The change was significant (p less than 0.001). The mechanism of this increase is unknown: it is important that there exists an increase in digitalis activity and not only a haematic elevation.