Abstract
1 The steady-state plasma concentrations of metoprolol and propafenone were determined in patients being treated with one of these drugs alone and during combined treatment with both drugs. In addition, single dose studies with metoprolol, propafenone and the combination of both drugs were performed in healthy volunteers to determine the pharmacokinetics and the time course of beta-adrenoceptor blocking activity. 2 In four patients being treated with metoprolol first and subsequently with propafenone in addition steady-state levels of metoprolol increased two to five fold with simultaneous treatment with propafenone. 3 In four patients being treated with the drug combination first and thereafter with propafenone alone no changes in the steady-state levels of propafenone were observed between both treatment periods. 4 Adverse effects of the drug combination were observed in two patients (one patient experienced severe nightmares and the other left ventricular failure). 5 When single oral doses of metoprolol (50 mg) and propafenone (150 mg) and the combination of both were administered to healthy subjects, an approximately two-fold decrease of the oral clearance of metoprolol was seen when propafenone was given in addition. No conclusive changes in the pharmacokinetics of propafenone could be detected in the presence of metoprolol. 6 Duration of beta-adrenoceptor blocking activity of a single dose of metoprolol in healthy volunteers as measured by reduction of exercise-induced tachycardia increased when propafenone was given in addition. 7 The dose of metoprolol should be reduced when propafenone is given in addition.
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- Briant R. H., Dorrington R. E., Ferry D. G., Paxton J. W. Bioavailability of metoprolol in young adults and the elderly, with additional studies on the effects of metoclopramide and probanthine. Eur J Clin Pharmacol. 1983;25(3):353–356. doi: 10.1007/BF01037947. [DOI] [PubMed] [Google Scholar]
- Connolly S. J., Kates R. E., Lebsack C. S., Harrison D. C., Winkle R. A. Clinical pharmacology of propafenone. Circulation. 1983 Sep;68(3):589–596. doi: 10.1161/01.cir.68.3.589. [DOI] [PubMed] [Google Scholar]
- Connolly S., Lebsack C., Winkle R. A., Harrison D. C., Kates R. E. Propafenone disposition kinetics in cardiac arrhythmia. Clin Pharmacol Ther. 1984 Aug;36(2):163–168. doi: 10.1038/clpt.1984.157. [DOI] [PubMed] [Google Scholar]
- Hege H. G., Hollmann M., Kaumeier S., Lietz H. The metabolic fate of 2H-labelled propafenone in man. Eur J Drug Metab Pharmacokinet. 1984 Jan-Mar;9(1):41–55. doi: 10.1007/BF03189604. [DOI] [PubMed] [Google Scholar]
- Hollmann M., Brode E., Hotz D., Kaumeier S., Kehrhahn O. H. Investigations on the pharmacokinetics of propafenone in man. Arzneimittelforschung. 1983;33(5):763–770. [PubMed] [Google Scholar]
- Kates R. E., Yee Y. G., Winkle R. A. Metabolite cumulation during chronic propafenone dosing in arrhythmia. Clin Pharmacol Ther. 1985 Jun;37(6):610–614. doi: 10.1038/clpt.1985.97. [DOI] [PubMed] [Google Scholar]
- Regårdh C. G., Johnsson G. Clinical pharmacokinetics of metoprolol. Clin Pharmacokinet. 1980 Nov-Dec;5(6):557–569. doi: 10.2165/00003088-198005060-00004. [DOI] [PubMed] [Google Scholar]
- Siddoway L. A., Roden D. M., Woosley R. L. Clinical pharmacology of propafenone: pharmacokinetics, metabolism and concentration-response relations. Am J Cardiol. 1984 Nov 14;54(9):9D–12D. doi: 10.1016/s0002-9149(84)80278-7. [DOI] [PubMed] [Google Scholar]
- Sklar J., Johnston G. D., Overlie P., Gerber J. G., Brammell H. L., Gal J., Nies A. S. The effects of a cardioselective (metoprolol) and a nonselective (propranolol) beta-adrenergic blocker on the response to dynamic exercise in normal men. Circulation. 1982 May;65(5):894–899. doi: 10.1161/01.cir.65.5.894. [DOI] [PubMed] [Google Scholar]