LACK OF A PHARMACOKINETIC INTERACTION BETWEEN CARVEDILOL AND DIGITOXIN OR PHENPROCOUMON

The possibility of a pharmacokinetic interaction between carvedilol an d digitoxin (Study I) or phenprocoumon (Study II) has been evaluated i n groups of 12 healthy volunteers. The bioavailability (C(max), t(max) , AUC) of digitoxin and phenprocoumon were assessed after a single dos e, given once alone and once on day 6 of treatment with carvedilol 25 mg o.d. C(max), t(max), AUC and U(t) of carvedilol and desmethylcarved ilol were also investigated after the fifth dose of carvedilol and aft er the sixth dose given concomitantly with digitoxin or phenprocoumon. In Study I, the 95 % confidence intervals of the ratio test versus th e reference findings were; digitoxin C(max) 0.80-1.20, t(max) 0.56-1.1 4, AUC 0.97-1.33, and for carvedilol C(max) 0.81-1.22; t(max) 0.66-1.2 3; AUC 0.91-1.17. Formation of the active metabolite desmethylcarvedil ol and the urinary recovery of carvedilol and desmethylcarvedilol were not influenced by digitoxin. In Study II C(max) and AUC of phenprocou mon were not changed after carvedilol. C(max) of carvedilol was decrea sed after phenprocoumon. The kinetic parameters of phenprocoumon were C(max) 0.80-1.05, t(max) 0.47-2.00, AUC 0.78-1.05, and for carvedilol C(max) 0.59-1.06, t(max) 0.71-1.73, AUC 0.80-1.08, respectively. The p lasma levels of desmethylcarvedilol and the urinary recovery of carved ilol and desmethylcarvedilol were not influenced by phenprocoumon. The blood pressure and heart rate after carvedilol alone were not affecte d by concomitant administration of digitoxin or phenprocoumon.