Silke B, Nelson G, Verma S P, Clarke J, Baliga G, Taylor S H
Clin Pharmacol Ther. 1985 Sep;38(3):266-72. doi: 10.1038/clpt.1985.169.
The hemodynamic dose-response effects of intravenous (25 and 50 mg) and oral (200 and 400 mg) acebutolol were compared in a randomized between-group study in men within 17 hours of an acute uncomplicated myocardial infarction. Six subjects were evaluated in each of the four groups. After a 1-hour control period, hemodynamic variables and plasma drug concentrations were determined at 15 (intravenous therapy only), 30, 60, 90, 120, and 240 minutes after dosing. At the doses studied, hemodynamic dose-response effects were not evident after either intravenous or oral acebutolol. In all groups acebutolol reduced systolic and mean systemic arterial pressure, heart rate, cardiac output, and stroke volume. Pulmonary artery occluded pressure and systemic vascular resistance were transiently increased. Maximum changes developed between 15 and 30 minutes after intravenous dosing and between 1 and 2 hours after oral dosing. However, there were substantial reductions in cardiac output (-0.7 L/min/m2; P less than 0.05) by 30 minutes after oral dosing. Effects lasted for 2 hours after intravenous dosing and for 4 hours after oral dosing. Our data confirm the hemodynamic safety of acebutolol after acute myocardial infarction. The relevance of the time-dependent hemodynamic differences between intravenous and oral initiation of beta-blockade to the overall goal of reducing myocardial oxygen requirements after acute coronary artery occlusion merits closer examination.
在一项针对急性非复杂性心肌梗死17小时内男性的随机组间研究中，比较了静脉注射（25毫克和50毫克）和口服（200毫克和400毫克）醋丁洛尔的血流动力学剂量反应效应。四个组每组评估6名受试者。在1小时的对照期后，在给药后15分钟（仅静脉治疗组）、30、60、90、120和240分钟测定血流动力学变量和血浆药物浓度。在所研究的剂量下，静脉注射或口服醋丁洛尔后血流动力学剂量反应效应均不明显。在所有组中，醋丁洛尔均降低收缩压和平均体动脉压、心率、心输出量和每搏量。肺动脉闭塞压和体循环血管阻力短暂升高。静脉给药后15至30分钟以及口服给药后1至2小时出现最大变化。然而，口服给药后30分钟心输出量显著降低（-0.7升/分钟/平方米；P<0.05）。静脉给药后效应持续2小时，口服给药后持续4小时。我们的数据证实了急性心肌梗死后醋丁洛尔的血流动力学安全性。静脉注射和口服β受体阻滞剂起始时随时间变化的血流动力学差异与急性冠状动脉闭塞后降低心肌需氧量的总体目标之间的相关性值得进一步研究。
