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

Aims The aim of this study was to examine the bioequivalence between a sing le oral dose of digoxin administered alone and with a coadministration of m acrogol 4000 (a laxative polymer) in 18 healthy volunteers. Methods This was an open, randomised, two-way cross-over study, with a sing le dose oral administration of 0.5 mg digoxin administered alone or in comb ination 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 o f digoxin AUC and a 40% decrease in its C-max (P<0.05). Digoxin t(max) and t(1/2,z) were nor 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 digox in pharmacokinetics. This is most likely due to a reduction of the intestin al absorption of digoxin. However, there was no consequence of this interac tion on heart rate and AV conduction.