Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man.
The haemodynamic effects of the selective beta1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selective beta1-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/l) prenalterol had to be administered in doses that were twelve times higher than before the beta-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.
D000318:Adrenergic beta-Agonists / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D011412:Propanolamines / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D008790:Metoprolol