LACK OF A PHARMACOKINETIC INTERACTION BETWEEN CARVEDILOL AND DIGITOXIN OR PHENPROCOUMON

The possibility of a pharmacokinetic interaction between carvedilol and digitoxin (Study I) or phenprocoumon (Study II) has been evaluated in groups of 12 healthy volunteers. The bioavailability (C(max), t(max), AUC) of digitoxin and phenprocoumon were assessed after a single dose, 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 desmethylcarvedilol were also investigated after the fifth dose of carvedilol and after the sixth dose given concomitantly with digitoxin or phenprocoumon. In Study I, the 95 % confidence intervals of the ratio test versus the reference findings were; digitoxin C(max) 0.80-1.20, t(max) 0.56-1.14, AUC 0.97-1.33, and for carvedilol C(max) 0.81-1.22; t(max) 0.66-1.23; AUC 0.91-1.17. Formation of the active metabolite desmethylcarvedilol and the urinary recovery of carvedilol and desmethylcarvedilol were not influenced by digitoxin. In Study II C(max) and AUC of phenprocoumon were not changed after carvedilol. C(max) of carvedilol was decreased 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 plasma levels of desmethylcarvedilol and the urinary recovery of carvedilol and desmethylcarvedilol were not influenced by phenprocoumon. The blood pressure and heart rate after carvedilol alone were not affected by concomitant administration of digitoxin or phenprocoumon.