Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man
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Summary
The haemodynamic effects of the selectiveβ1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selectiveβ1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/1) prenalterol had to be administered in doses that were twelve times higher than before theβ-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.
Key-words
prenalterol metoprolol haemodynamics pharmacokineticsPreview
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References
- 1.Åblad, B., Borg, K. O., Carlsson, E., Johnsson, G., Malmfors, T., Regårdh, C.-G.: Animal and human pharmacological studies on metoprolol — a new selective adrenergicβ 1-receptor antagonist. Acta pharmacol. toxicol. (Kbh)36, Suppl V (1975)Google Scholar
- 2.Carlsson, E., Dahlöf, C.-G., Hedberg, A.: Differentiation of cardiac chronotropic and inotropic effects ofβ-adrenoceptor agonists. Naunyn Schmiedebergs Arch. Pharmacol.300, 101–105 (1977)Google Scholar
- 3.Ervik, M.: Quantitative determination of metoprolol in plasma and urine by gas chromatography. Acta pharmacol. toxicol. (Kbh)36, Suppl V, 136–144 (1975)Google Scholar
- 4.Johnsson, G., Regårdh, C.-G., Sölvell, L.: Combined pharmacokinetic and pharmacodynamic studies in man of the adrenergicβ 1-receptor antagonist metoprolol. Acta pharmacol. toxicol. (Kbh)36, Suppl V, 31–44 (1975)Google Scholar
- 5.Johnsson, G., Jordö, L., Lundborg, P., Rönn, O., Welin-Fogelberg, I., Wikstrand, J.: Haemodynamic and tolerance studies in man of a new, orally active, selectiveβ 1-adrenoceptor agonist H 80/62. Europ. J. clin. Pharmacol.13, 163–170 (1978)Google Scholar
- 6.Knaus, M., Pfister, B., Dubach, U. C., Imhof, P. R.: Humanpharmacology studies with a new, orally active stimulant of cardiac adrenergicβ-receptors (C50,005/A-Ba). Am. Heart J.95, 602–610 (1978)Google Scholar
- 7.Sedman, A. J., Wagner, J. G.: CSTRIP, a Fortran IV computer program for obtaining initial polyexponential parameter estimates. J. Pharm. Sci.65, 1006–1010 (1976)Google Scholar
- 8.Tuttle, R. R., Mills, J.: Development of a new catecholamine to selectively increase cardiac contractility. Circ. Res.36, 185–196 (1975)Google Scholar
- 9.Weissler, A. M., Harris, W. S., Schoenfeld, C. D.: Bedside technichs for the evaluation of ventricular function in man. Am. J. Cardiol.23, 577–583 (1969)Google Scholar
- 10.Wikstrand, J., Berglund, G., Wilhelmsen, L., Wallentin, I.: Value of systolic and diastolic time intervals. Br. Heart J.40, 256–267 (1978)Google Scholar