Löfdahl C G, Dahlöf C, Westergren G, Olofsson B, Svedmyr N
Department of Clinical Pharmacology, University of Göteborg, Sweden.
Eur J Clin Pharmacol. 1988;33 Suppl:S25-32. doi: 10.1007/BF00578409.
The beta 2-adrenoceptor mediated effects on ventilatory capacity, forced expiratory volume in one second (FEV1), forced ventilatory capacity (FVC), heart rate, and skeletal muscle tremor of a new controlled-release (CR) formulation of metoprolol, 100 mg and 200 mg, and of atenolol tablets, 100 mg, were studied in eight asthmatic patients. The effects of single-dose treatment, including placebo as reference, were studied in a randomized, double-blind, cross-over design. Starting 2 h after drug intake, four intravenous infusions containing increasing doses of terbutaline were given at 30-min intervals, followed by three doses of terbutaline inhalations. Maximum plasma concentrations for both metoprolol and atenolol were achieved within the study period. The FEV1 measurements after terbutaline infusions and inhalations were significantly lower after atenolol than after either dose of metoprolol CR. This indicates less blockade of beta 2-adrenoceptors with metoprolol CR than with atenolol at maximum plasma concentrations. The terbutaline-induced skeletal muscle tremor and increase in heart rate were less after atenolol than after either dose of metoprolol CR, also suggesting less interaction of metoprolol CR with beta 2-receptors. Thus, the new CR formulation of metoprolol caused fewer adverse effects on beta 2-adrenoceptor mediated bronchodilatation than a clinically equivalent dose of atenolol.
在8名哮喘患者中研究了100毫克和200毫克美托洛尔新控释（CR）制剂以及100毫克阿替洛尔片对通气能力、一秒用力呼气量（FEV1）、用力通气量（FVC）、心率和骨骼肌震颤的β2 - 肾上腺素能受体介导的作用。采用随机、双盲、交叉设计研究了单剂量治疗的效果，包括以安慰剂作为对照。在服药后2小时开始，每隔30分钟静脉输注4次含递增剂量特布他林的溶液，随后进行3次特布他林吸入治疗。在研究期间达到了美托洛尔和阿替洛尔的最大血浆浓度。阿替洛尔治疗后，特布他林输注和吸入后的FEV1测量值显著低于任何一种剂量的美托洛尔CR治疗后。这表明在最大血浆浓度下，美托洛尔CR对β2 - 肾上腺素能受体的阻断作用小于阿替洛尔。阿替洛尔治疗后，特布他林引起的骨骼肌震颤和心率增加低于任何一种剂量的美托洛尔CR，这也表明美托洛尔CR与β2受体的相互作用较小。因此，与临床等效剂量的阿替洛尔相比，新的美托洛尔CR制剂对β2 - 肾上腺素能受体介导的支气管扩张产生的不良反应更少。
