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

Author(s): Ragueneau I, Poirier JM, Radembino N, Sao AB, Funck-Brentano C, Jaillon P

Affiliation(s): Clinical Pharmacology Unit and Department of Pharmacology, Saint-Antoine University Hospital, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France.

Publication date & source: 1999-09, Br J Clin Pharmacol., 48(3):453-6.

Publication type: Clinical Trial; Randomized Controlled Trial

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 Cmax (P<0.05). Digoxin tmax and t1/2,z 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.