Hemodynamic effects of brefanolol and propranolol assessed by noninvasive methods in patients with arterial hypertension
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Brefanolol, a novel beta-blocker, shows promise for hypertension. Lower doses (50mg) offer a balanced effect of beta-adrenergic blockade and vasodilation, suggesting improved therapeutic potential compared to higher doses or propranolol.
Area of Science:
- Cardiovascular Pharmacology
- Clinical Hypertension Research
Background:
- Arterial hypertension (WHO stages I and II) requires effective therapeutic agents.
- Beta-adrenergic blocking agents are a cornerstone of hypertension management.
- Novel agents with vasodilating properties may offer improved hemodynamic profiles.
Purpose of the Study:
- To evaluate the hemodynamic effects of brefanolol, a novel beta-adrenergic blocking agent with vasodilating properties.
- To compare the effects of different doses of brefanolol (50 mg and 100 mg) against placebo and propranolol in patients with arterial hypertension.
- To determine the optimal dose of brefanolol for a balanced hemodynamic response.
Main Methods:
- A placebo-controlled, randomized, cross-over study involving 16 patients with arterial hypertension.
- Administration of single oral doses of placebo, 80 mg propranolol, 50 mg brefanolol, and 100 mg brefanolol.
- Noninvasive assessment of hemodynamic parameters including blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance using mechano- and impedance cardiography and venous occlusion plethysmography.
- Serial measurements taken at 2, 4, 6, 10, and 24 hours post-administration.
Main Results:
- Propranolol induced typical beta-blocker effects: reduced blood pressure, heart rate, cardiac output, stroke volume, and increased total peripheral resistance.
- 100 mg of brefanolol produced hemodynamic effects comparable to propranolol.
- 50 mg of brefanolol significantly decreased blood pressure, heart rate, and cardiac output, while increasing stroke volume and reactive hyperemia, indicating a more balanced vasodilating and beta-blocking profile.
Conclusions:
- Brefanolol demonstrates both beta-adrenergic blocking and vasodilating properties in patients with hypertension.
- The 50 mg dose of brefanolol appears to offer a more favorable balance between its vasodilating and beta-adrenergic blocking effects compared to the 100 mg dose.
- Dose titration of brefanolol suggests potential for a balanced hemodynamic profile in managing arterial hypertension.
Abstract:
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.