A 1-WEEK DOSE-RANGING STUDY OF INHALED SALMETEROL IN PATIENTS WITH ASTHMA

Study objective: A dose-ranging study was conducted to evaluate the efficacy and safety of a new long-acting, selective beta(2)-adrenoceptor agonist, salmeterol. Design: Adolescents and adults (N=160) with mild-to-moderate asthma received salmeterol (10.5, 21, 42, or 84 mu g) or placebo by metered-dose inhaler twice daily for 1 week. Twelve-hour serial spirometry measurements were performed on the first and last dais of treatment, and patients recorded their peak-expiratory now (PEF) twice daily on diary cards. Results: On day 1, salmeterol produced greater bronchodilation than placebo (p=0.001), and both the 42-mu g and 84-mu g doses of salmeterol were significantly more effective in improving FEV(1) responses than the two lower doses of salmeterol (p<0.05). After 1 week of treatment, all but the 21-mu g dose of salmeterol remained statistically superior to placebo (p<0.01), but significant differences between salmeterol doses were no longer evident, despite an apparent dose-response effect. Only the 42-mu g and 84-mu g doses of salmeterol sustained bronchodilation for 12 h in the majority of patients at both treatment days. The degree of improvement in morning and evening PEF was also found to be dose related. There was no significant difference among treatment groups in the overall incidence of events; however, pharmacologically predictable leg, tremor) occurred significantly more often with salmeterol, 84 mu g. Conclusions: Salmeterol, 42 mu g, was similar in efficacy to 84 mu g but was associated with a lower incidence of adverse events. Salmeterol, 42 mu g twice daily, is a safe and effective dosage for patients with mild-to-moderate asthma who are persistently symptomatic and require maintenance bronchodilator therapy.