Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers.
OBJECTIVE
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.
Ragueneau
I
I
Clinical Pharmacology Unit and Department of Pharmacology, Saint-Antoine University Hospital, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France.
Poirier
J M
JM
Radembino
N
N
Sao
A B
AB
Funck-Brentano
C
C
Jaillon
P
P
D000328:Adult; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002400:Cathartics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology*
D002316:Cardiotonic Agents; D002400:Cathartics; D011092:Polyethylene Glycols; D004077:Digoxin