Drug interactions with cardiac glycosides: evaluation of a possible digoxin-ethmozine pharmacokinetic interaction

Problems in studying pharmacokinetic interactions with digoxin were evaluated using as a test model the examination of a possible interaction between digoxin and ethmozine in a group of 11 patients with cardiac disease. A single-blind, placebo-controlled, nonrandomized protocol design was used. Considerable intrapatient variability in day-to-day serum digoxin levels was documented that could not be accounted for by laboratory variability in digoxin assay measurements (mean coefficient of variation 10.1%) or alterations in blood urea nitrogen (BUN), serum creatinine, or body weight during the course of the study. No consistent, statistically significant alteration of mean serum digoxin levels occurred when the baseline, placebo, and ethmozine phases were compared, although the study design would have permitted detection of a 0.29-ng/ml alteration in mean serum digoxin levels. A discussion of the sources of variability in digoxin levels is provided.