Weinstein S, Chervinsky P, Pollard S J, Bronsky E A, Nathan R A, Prenner B, Howland W C, Stahl E, Liddle R
Allergy and Asthma Specialists, Medical Group, Huntington Beach, California 92647, USA.
J Asthma. 1997;34(1):43-52. doi: 10.3109/02770909709071202.
This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 micrograms and 42 micrograms administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral beta-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vital signs, electrocardiogram (ECG), and 24-hr ECG (Holter) monitoring. Both the 21-micrograms and 42-micrograms doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV1) (p < or = 0.02) and PEFR (p < or = 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-micrograms dosage producing consistently higher serial FEV1 and PEFR than did the 21-micrograms dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p < or = 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECGs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 micrograms or 42 micrograms twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 micrograms twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 micrograms.
这是一项为期1周的研究，旨在评估两种沙美特罗剂量方案对哮喘儿童的安全性和有效性。共有243名4至11岁的轻度至中度哮喘儿童参加了一项随机、双盲、安慰剂对照、平行组、多中心研究，该研究评估了通过定量吸入器（MDI）每日两次给予21微克和42微克昔萘酸沙美特罗，持续1周。患者可根据需要使用沙丁胺醇MDI缓解急性症状。在研究期间可继续使用固定剂量的吸入性糖皮质激素和/或色甘酸钠，但不允许使用茶碱和口服β受体激动剂。在治疗的第1天和第8天对6至11岁的患者进行12小时连续肺功能测定（肺活量测定），对所有患者进行连续呼气峰值流速（PEFR）测定；在吸入研究药物前每天记录早晚的PEFR。通过监测不良事件、临床实验室值、生命体征、心电图（ECG）和24小时动态心电图（Holter）监测来评估安全性。在第1天和第8天，与安慰剂相比，21微克和42微克剂量的沙美特罗通过12小时连续1秒用力呼气量（FEV1）（p≤0.02）和PEFR（p≤0.001）测量，产生了显著更大的支气管扩张。观察到一个小的剂量反应，42微克剂量的沙美特罗产生的连续FEV1和PEFR始终高于21微克剂量，尽管差异无统计学意义。与安慰剂相比，两种剂量的沙美特罗早晚PEFR均显著增加（p≤0.008）。12名患者（5%）经历了可能与药物相关的不良事件，其中头痛最为常见（每个沙美特罗组均为4%）。用任何一种剂量的沙美特罗治疗后，通过Holter监测、心电图、生命体征或临床实验室值测量的心率均无临床显著变化。每日两次21微克或42微克的沙美特罗对4至11岁儿童产生支气管扩张有效，且两种剂量的安全性均良好。与接受21微克沙美特罗的患者相比，每日两次接受42微克沙美特罗治疗的患者在哮喘控制方面有更大改善的趋势。
