Bauer K, Brunner-Ferber F, Distlerath L M, Lippa E A, Binkowitz B, Till P, Kaik G
Division of Internal Medicine I, University of Vienna Medical School, Austria.
Clin Pharmacol Ther. 1991 Jun;49(6):658-64. doi: 10.1038/clpt.1991.83.
Systemic beta-blockade after single doses of ophthalmic beta-blockers (one drop in each eye) was investigated in healthy volunteers in two randomized, double-blind, crossover, placebo-controlled studies. beta-Blockade was evaluated by displacement of the bronchodilator (specific airway conductance), positive chronotropic (heart rate), and tremorogenic (finger tremor amplitude) dose-response curve for inhaled isoproterenol. In study 1, 0.5% betaxolol, 0.6% metipranolol, and 0.5% timolol were tested in 16 subjects. Compared with placebo, all beta-blockers resulted in a significant systemic beta-blockade (p greater than 0.05); the increasing order of potency was betaxolol, metipranolol, and timolol. In study 2, 2% butylamino-phenoxy-propanol-acetate (BPPA; a noncardioselective but topically oculoselective drug) and 1% timolol were investigated in 12 subjects. Placebo and BPPA showed no differences (p greater than 0.05), whereas timolol resulted in a significant beta-blockade (p less than 0.05). Topical oculoselectivity is an important aspect of drug safety of beta-blocking eyedrops. Measure of tremor is appropriate to evaluate beta 2-blockade.
在两项随机、双盲、交叉、安慰剂对照研究中，对健康志愿者单剂量使用眼科β受体阻滞剂（每只眼滴一滴）后的全身β受体阻滞情况进行了研究。通过吸入异丙肾上腺素的支气管扩张剂（比气道传导率）、正性变时（心率）和致震颤（手指震颤幅度）剂量反应曲线的位移来评估β受体阻滞。在研究1中，对16名受试者测试了0.5%倍他洛尔、0.6%美替洛尔和0.5%噻吗洛尔。与安慰剂相比，所有β受体阻滞剂均导致显著的全身β受体阻滞（p>0.05）；效力递增顺序为倍他洛尔、美替洛尔和噻吗洛尔。在研究2中，对12名受试者研究了2%丁胺苯氧基丙醇醋酸酯（BPPA；一种非心脏选择性但局部眼选择性药物）和1%噻吗洛尔。安慰剂和BPPA无差异（p>0.05），而噻吗洛尔导致显著的β受体阻滞（p<0.05）。局部眼选择性是β受体阻滞眼药水药物安全性的一个重要方面。震颤测量适用于评估β2受体阻滞。
