Medicine of the Future in America

A 1-Week Dose-Ranging Study of Inhaled Salmeterol in Patients With Asthma: Spirometric Assessments of Efficacy

A covariate analysis of the serial FEVi values was performed to adjust for these differences in baseline characteristics.
Figure 1 illustrates the unadjusted mean percent change in FEVi on treatment days 1 and 8. After 12 h postdosing on treatment day 1, patients receiving the two higher doses of salmeterol still had mean improvements in FEVi >20 percent above baseline. Each of the salmeterol treatments produced significantly greater bronchodilation than placebo (p=0.001), and the 42-jug or 84-ng dose produced significantly greater responses than the two lower doses (p<0.023). On treatment day 8, all but the 21-tig dose of salmeterol remained significantly better than placebo (p<0.006). The four salmeterol groups had considerably higher predose FEVi values than those established at baseline 1 week earlier, with the 42-/ng group showing the greatest increase (27 percent). All salmeterol treatments produced mean FEVi responses >15 percent above baseline values throughout the 12 h of evaluation. However, no statistically significant differences between the salmeterol doses were observed on the last day of treatment.
When a covariate analysis was performed to correct for any differences in the baseline characteristics of the treatment groups, a dose-response relationship was again clearly seen on treatment day 1 (Fig 2). At nearly every time point, salmeterol 84 /ig, had a significantly greater effect than either the 10.5- or 21-fig doses, while the 42-^g dose produced significantly greater FEVi responses than the 10.5-dose or the 21-/? dose (at hours 10 and 12) more buy inhalers online. No differences were detected between the 10.5-/xg and 21-/tig doses or between the 42-^g and 84-/ug doses on treatment days 1 or 8. Table 2 presents the number of patients who maintained an FEVi response of at least 15 percent above baseline for 12 h postdose. Only the 42-/ng and 84-/xg doses of salmeterol consistently sustained bronchodilation in greater than 50 percent of patients for 12 h. Area under the FEVi curve (AUC), which provides a measure of both degree and duration of bronchodilation, was significantly different among groups on treatment day 1, with the 42-/ig and 84-/*g doses of salmeterol producing the greatest effect (Table 3).
Serial FVC and FEF25-75% determinations produced similar patterns as those for FEVi with respect to the effect of the different doses.

Figure-1

Figure 1. Mean percent change from predose FEVi on treatment days 1 and 8.

Figure-2

Figure 2. Mean FEV i responses from a covariate analysis to correct for possible differences in baseline characteristics of treatment groups.

Table 2—Number (Percent) of Patients With FEVi at Least 15 Percent Above Baseline 12 h After Dosing

TreatmentDay Placebo Salmeterol, g
10.5 21 42 84
18 4/35(11) 7/31(23) 12/29 (41) 15/29 (52) 10/32(31) 13/32(41) 20/33 (61) 16/31(52) 18/31 (58) 15/28 (54)

Table 3—Mean Area Under the FEVi Curve

TreatmentDay Placebo Salmeterol, /ug p Value
10.5 21 42 84
1 0.3 1.7 1.6 3.3 3.8 0.001
8 1.6 3.2 2.8 4.6 3.8 0.166
This entry was posted in Asthma and tagged asthma, bronchodilator, salmeterol, theophylline.
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