Effect of cisapride and metoclopramide on digoxin bioavailability

Pharmacokinetics of digoxin were investigated in six healthy volunteers following one week of digoxin monotherapy 0.25 mg b.i.d., and during coadministration of metoclopramide 10 mg t.i.d. or cisapride 10 mg t.i.d.. Metoclopramide reduced the peak plasma concentration of digoxin from 1.5 +/- 0.2 ng/ml to 1.1 +/- 0.1 ng/ml (mean +/- SEM) (p = 0.05), cisapride lowered the peak concentration to 1.3 +/- 0.1 ng/ml (p = 0.14). Metoclopramide prolonged the time required to reach the peak concentration of digoxin from 2 hr to 2.7 hr (p = 0.17), cisapride did not. Digoxin AUC0-12 (743 +/- 79 ng/ml.min) was reduced by 12% on coadministration of cisapride (653 +/- 38 ng/ml.min, p = 0.22) and by 19% on coadministration of metoclopramide (605 +/- 34 ng/ml.min, p = 0.06). It is concluded that the gastrointestinal absorption of digoxin is reduced by both substances. Monitoring of the patient's clinical status should be recommended when metoclopramide and cisapride are coadministered.