van den Berg B T, Smeets J J, van Boxtel C J, Maesen F P
Department of Clinical Pharmacology and Pharmacotherapy, University of Amsterdam, Netherlands.
Fundam Clin Pharmacol. 1995;9(6):593-603. doi: 10.1111/j.1472-8206.1995.tb00538.x.
Administration of different doses of formoterol from a recently developed multiple dose dry powder device was tested in a placebo-controlled, single-centre, double-blind, within-patient trial. Eighteen patients of both sexes, aged 18-65 years, with a FEV1 of 50-80% and a reversibility of at least 15% were randomized. During four treatment periods of 8 days each, divided by approximately 6 days, patients received placebo or 6, 12 or 24 micrograms (PL, F6, F12 and F24, respectively) of formoterol from the powder device. Efficacy parameters (FEV1) and safety parameters (primarily pulse rate, electrocardiogram [ECG] and subjective experiences) were evaluated during 24 hours on the last day of each treatment period. Peak flow and the number of puffs of used rescue medication (100 micrograms of salbutamol) were registered during treatment periods. For efficacy analysis, 17 patients remained. For FEV1 0.5 hour before the last dose and 12 and 24 hours after the last dose all formoterol doses were statistically significant superior to placebo. Clinically relevant differences from placebo were found up to 8 hours (F6) and 12 hours (F12 and F24). The difference between doses was clinically relevant for the area under the FEV1 curve between F6 and F24. PEF on the treatment days corresponded to these findings. In three cases of 13 reported adverse effects, the relation to trial medication was probable (tremor) or possible (insomnia and hyperaesthesia). All other safety measurements showed no significant differences. We conclude that formoterol dry powder in the newly developed multiple dose inhalation device is an effective and safe beta 2-stimulant with a long duration of action in doses of 6, 12 and 24 micrograms. The 24 micrograms dose is superior to the 6 micrograms dose. Efficacy decreased considerably between the 12th and 24th hour after dosing.
在一项安慰剂对照、单中心、双盲、患者自身对照试验中，对一种新开发的多剂量干粉装置给予不同剂量的福莫特罗进行了测试。18名年龄在18至65岁之间、FEV1为50%至80%且可逆性至少为15%的男女患者被随机分组。在四个为期8天的治疗期内，每隔约6天，患者从干粉装置中接受安慰剂或6、12或24微克（分别为PL、F6、F12和F24）的福莫特罗。在每个治疗期的最后一天的24小时内评估疗效参数（FEV1）和安全性参数（主要是脉搏率、心电图[ECG]和主观感受）。在治疗期间记录峰值呼气流速和使用的急救药物（100微克沙丁胺醇）的吸入次数。为进行疗效分析，17名患者纳入研究。对于最后一剂前0.5小时以及最后一剂后12小时和24小时的FEV1，所有福莫特罗剂量在统计学上均显著优于安慰剂。在长达8小时（F6）和12小时（F12和F24）时发现与安慰剂存在临床相关差异。F6和F24之间FEV1曲线下面积的剂量差异具有临床相关性。治疗日的峰值呼气流速与这些结果相符。在报告的13例不良反应中，3例与试验药物可能相关（震颤）或可能相关（失眠和感觉过敏）。所有其他安全性测量均无显著差异。我们得出结论，新开发的多剂量吸入装置中的福莫特罗干粉是一种有效且安全的β2激动剂，6、12和24微克剂量的作用持续时间长。24微克剂量优于6微克剂量。给药后12小时至24小时疗效显著下降。
