Summary
Pharmacokinetics of metoprolol, propranolol, and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs, and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (P<0.05). The plasma level time curve (AUC) of the two above-mentioned beta blockers behaved similarly (P<0.05). Other kinetic parameters of these two drugs were not influenced to a statistically significant extent by cimetidine, despite the tendency for the elimination half-life of metoprolol and propranolol to be prolonged when cimetidine is added. Measurement of exercise-induced tachycardia on the sixth day of administration showed no differences between monotherapy with the beta blockers and combined treatment with each of them together with cimetidine. Apart from one volunteer who complained of anxiety, weakness, and sweating on the sixth day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers, nor during monotherapy with beta blockers.
Zusammenfassung
Die Pharmakokinetik von Metoprolol, Propranolol und Atenolol wurde nach jeweils 7tägiger oraler Monotherapie mit diesen Substanzen und nach 7tägiger kombinierter Gabe jedes Betablockers zusammen mit Cimetidin bei 6 gesunden Probanden geprüft. Cimetidinapplikation führte zu keiner Änderung des kinetischen Verhaltens von Atenolol. Demgegenüber stiegen nach Cimetidingabe die maximalen Metoprolol-Plasmaspiegel durchschnittlich um 70% und die von Propranolol um 95% im Vergleich zur Monotherapie mit diesen beiden Betablockern an (P<0,05). Ähnlich verhielt sich die AUC beider Betablocker unter zusätzlicher Therapie von Cimetidin (P<0,05). Bis auf einen geringen, jedoch nicht signifikanten Anstieg der Eliminationshalbwertzeit von Metoprolol und Propranolol bei gleichzeitiger Cimetidingabe wurden andere kinetische Parameter dieser beiden Pharmaka durch Cimetidin nicht bemerkenswert verändert. Die am 6. Tag jeder Behandlungsphase gemessene Hemmung der belastungsabhängigen Tachykardie ergab keine signifikanten Unterschiede zwischen der Monotherapie mit den jeweiligen Betablockern und deren kombinierter Gabe mit Cimetidin. Außer einem Probanden, der am 6. Tag der Therapie mit Metoprolol und Cimetidin über Angstgefühl, Schwäche und Schweißausbruch klagte, wurden weder in der Behandlungsperiode von Cimetidin mit den 3 Betablockern noch in den Monotherapiephasen Nebenwirkungen beobachtet.
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Supported by the Deutsche Forschungsgemeinschaft and the Dr. Robert Pfleger Stiftung, Bamberg
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Kirch, W., Spahn, H., Köhler, H. et al. Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine. Klin Wochenschr 60, 1401–1407 (1982). https://doi.org/10.1007/BF01716245
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DOI: https://doi.org/10.1007/BF01716245