Halabi A, Endell W, Halabi I, Kirch W
I. Medizinische Klinik, Christian-Albrechts-Universität, Kiel, F.R.G.
J Cardiovasc Pharmacol. 1990 Jul;16(1):81-6. doi: 10.1097/00005344-199007000-00011.
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.
在一项安慰剂对照、随机、交叉研究中，对16例动脉高血压患者（WHO I期和II期，10例男性，6例女性；年龄50.6±10.4岁；体重74.5±8.9 kg；均值±标准差）单次口服安慰剂、80 mg普萘洛尔以及50 mg和100 mg布瑞诺洛尔（一种具有血管舒张特性的β-肾上腺素能阻滞剂），以确定产生的血流动力学效应。在给药前以及给药后2、4、6、10和24小时，通过机械和阻抗心动图以及静脉闭塞体积描记法对血压、心率和各种血流动力学参数进行无创评估。普萘洛尔治疗导致了β-肾上腺素能阻滞剂引起的典型血流动力学变化，其特征为血压、心率、心输出量、每搏输出量显著降低，总外周阻力增加。100 mg布瑞诺洛尔的剂量也导致了类似的血流动力学效应。50 mg布瑞诺洛尔也使血压、心率和心输出量出现类似的显著下降，但每搏输出量和反应性充血增加。因此，在药物研发的这个阶段，50 mg和100 mg布瑞诺洛尔的剂量滴定表明，较低剂量在其β-肾上腺素能阻滞和血管舒张特性之间产生了更平衡的关系。
