Intersubject Variation in Absorption of Digoxin in Normal Volunteers

Abstract

The absorption of oral digoxin preparations was evaluated following single‐dose administration of 0.5mg of digoxin to 16 normal volunteers in a randomized crossover design. Absorption was estimated using the cumulative excretion of digoxin in urine for 7 days and the area under the 24‐hr serum digoxin concentration curve (AUC). Significant intersubject variability was observed with both parameters, but this variability was greater for the AUC. After intravenous administration, the 7‐day digoxin excretion was 68% of the dose. The elixir and a rapid dissolution tablet were significantly better absorbed (84.5 and 77.8%, respectively) than was a slow dissolution tablet (66.7%), as reflected by the fraction of the amount excreted in the urine following intravenous administration of the same dose. There was a highly significant correlation between the cumulative digoxin excretion in urine during the first 2 days compared to 7 days (r = +0.972, p < 0.001). Bioavailability of oral digoxin preparations can be reliably determined by comparison of the cumulative 2‐day excretion of digoxin following a single dose.