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.