Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers

Abstract

Aims. The aim of this study was to examine the bioequivalence between a single oral dose of digoxin administered alone and with a coadministration of macrogol 4000 (a laxative polymer) in 18 healthy volunteers. Methods. This was an open, randomised, two-way cross-over study, with a single dose oral administration of 0.5 mg digoxin administered alone or in combination with macrogol 4000, 20 g day-1 during 8 days. Pharmacokinetics of digoxin, heart rate and PR ECG interval at rest were assessed. Results. Macrogol 4000 coadministration was associated with a 30% decrease of digoxin AUC and a 40% decrease in its C(max) (P < 0.05). Digoxin t(max) and t(1,2α) were not significantly altered. Heart rate and PR interval did not differ during the two therapeutic sequences, digoxin alone and digoxin in combination. Conclusions. Macrogol 4000 coadministration interacts with single-dose digoxin pharmacokinetics. This is most likely due to a reduction of the intestinal absorption of digoxin. However, there was no consequence of this interaction on heart rate and AV conduction.