Effect of metoclopramide on digoxin absorption from tablets and capsules

The effect of metoclopramide, a drug that increases gut motility, on the consistency of digoxin absorption was examined in 16 healthy men. Each received the following four single-dose digoxin treatments in complete crossover fashion: two 0.25-mg digoxin tablets alone, two 0.25-mg tablets with metoclopramide, two 0.2-mg digoxin capsules alone, and two 0.2-mg digoxin capsules with metoclopramide. Mean serum AUCs over 24 hr (AUC-24) and cumulative urinary digoxin excretion over 48 hr (CUE-48) were of the same order for the tablets and capsules alone treatments. Metoclopramide reduced the mean AUC-24 for tablets from 12.26 ± 2.70 to 9.38 ± 3.78 ng · hr/ml (P < 0.001) and the CUE-48 from 119.0 ± 22.4 to 97.6 ± 22.2 µg (P < 0.01). There were no significant differences in mean AUC-24 (12.94 ± 3.16 and 13.45 ± 2.33 ng · hr/ml) and mean CUE-48 (117.8 ± 23.4 and 109.7 ± 25.0 µg) when capsules alone were compared to capsules with metoclopramide. Metoclopramide reduced the time to reach peak concentration for both digoxin dosage forms. The effect of metoclopramide on digoxin absorption is minimized by administration of digoxin in capsules. Clinical Pharmacology and Therapeutics (1984) 36, 724–730; doi:10.1038/clpt.1984.249