Hemodynamic effects of brefanolol and propranolol assessed by noninvasive methods in patients with arterial hypertension.
In a placebo-controlled, randomized, cross-over study, 16 patients (10 males, 6 females; 50.6 +/- 10.4 years; body weight of 74.5 +/- 8.9 kg; mean +/- SD) with arterial hypertension (WHO stages I and II) were administered single oral doses of placebo, 80 mg of propranolol, as well as 50 and 100 mg of brefanolol (a beta-adrenergic blocking agent with vasodilating properties) in order to determine the resulting hemodynamic effects. Blood pressure, heart rate, and various hemodynamic parameters were assessed noninvasively by mechano- and impedance cardiography as well as by venous occlusion plethysmography before and 2, 4, 6, 10, and 24 h after drug administration. Treatment with propranolol resulted in the typical hemodynamic changes induced by a beta-adrenergic blocking agent characterized by a significant reduction in blood pressure, heart rate, cardiac output, stroke volume, and an increase in total peripheral resistance. A dose of 100 mg of brefanolol also led to comparable hemodynamic effects. Similar significant decreases in blood pressure, heart rate, and cardiac output also occurred with 50 mg of brefanolol, but stroke volume and reactive hyperemia increased. Thus, in this phase of drug development, dose titration with 50 and 100 mg of brefanolol indicates that the lower dose gives rise to a more balanced relationship between its beta-adrenergic blocking and vasodilating properties.
Halabi
A
A
I. Medizinische Klinik, Christian-Albrechts-Universität, Kiel, F.R.G.
Endell
W
W
Halabi
I
I
Kirch
W
W
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002307:Cardiography, Impedance; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D014665:Vasodilator Agents; C065350:brefanolol; D011433:Propranolol