Summary
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 (Cmax, tmax, 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. Cmax, tmax, AUC and Ut 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 Cmax 0.80–1.20, tmax 0.56–1.14, AUC 0.97–1.33, and for carvedilol Cmax 0.81–1.22; tmax 0.66–1.23; AUC 0.91–1.17. Formation of the active metabolite desmethylcarvedilol and the urinary recovery of carvedilol and esmethylcarvedilol were not influenced by digitoxin.
In Study II Cmax and AUC of phenprocoumon were not changed after carvedilol. Cmax of carvedilol was decreased after phenprocoumon. The kinetic parameters of phenprocoumon were Cmax 0.80–1.05, tmax 0.47–2.00, AUC 0.78–1.05, and for carvedilol Cmax 0.59–1.06, tmax 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.
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References
Bartsch W, Sponer G, Strein K, Müller-Beckmann B, Kling L, Böhm E, Martin U, Borbe HO (1990) Pharmacological characteristics of the stereoisomers of carvedilol Eur J Clin Pharmacol 38 [Suppl 2]: 104–106
Braitman LE (1988) Confidence intervals extract clinically useful information from data. Ann Int Med 108: 296–298
De Mey C, Brendel E, Enterling D (1990) Carvedilol increases the systemic bioavailability of oral digoxin. Br J Clin Pharmacol 29: 486–490
Kitteringham NR, Büstgens L, Brundert E, Mineshita S, Ohnhaus EE (1983) Pharmacokinetics of phenprocoumon in patients with liver cirrhosis. Br J Clin Pharmacol 12 [Suppl]: 590P
Neugebauer G, Akpan W, von Moellendorff E, Reiff K (1987) Pharmacokinetics and disposition of carvedilol in humans. J Cardiovasc Pharmacol 10 [Suppl 1]: 85–89
Reiff K (1987) High performance liquid chromatography for the determination of carvedilol and its desmethyl metabolite in body fluids. J Chromatogr 413: 355–360
Schloos J, Reiff K, Schulz J, Belz GG (1992) The course of β1 and α1-adrenoceptor blocking activities after oral administration of carvedilol to healthy volunteers. Naunyn-Schmiedebergs Arch Pharmacol 345 [Suppl]: P329
Steinijans VW, Hartmann M, Huber R, Radtke HW (1991) Lack of pharmacokinetic interaction as an equivalence problem. Int J Clin Pharm Ther Tox 29: 323–328
Steinijans VW, Diletti E (1983) Statistical analysis of bioavailability studies: parametric and nonparametric confidence intervals. Eur J Clin Pharmacol 24: 127–131
Spahn H, Kirch W, Mutschler F, Ohnhaus EE, Kitteringham NR, Lögering HJ, Paar J (1984) Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol. Br J Clin Pharmacol 17: 97S-102S
Sponer G, Bartsch W, Strein K, Müller-Beckmann B, Böhm E (1987) Pharmacological profile of carvedilol as a beta-blocking agent with vasodilating and hypotensive properties. J Cardiovasc Pharmacol 9: 317–327
Wood A, Feely J (1983) Pharmacokinetic drug interactions with propranolol. Clin Pharmacokinet 8: 253–262
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Harder, S., Brei, R., Caspary, S. et al. Lack of a pharmacokinetic interaction between carvedilol and digitoxin or phenprocoumon. Eur J Clin Pharmacol 44, 583–586 (1993). https://doi.org/10.1007/BF02440864
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DOI: https://doi.org/10.1007/BF02440864