Bronchodilating effects of salmeterol, theophylline and their combination in patients with moderate to severe asthma

Ten patients with moderate to severe asthma (mean FEV1±SD: 57.3±5.8% of predicted) participated in this 4-day single-blind, placebo-controlled, crossover study, aimed to comparatively evaluate the bronchodilating effects of a single dose of inhaled salmeterol (50 μg) and oral slow-release theophylline (Theo-Dur, 600 mg tablets), used either alone or in combination. In particular, FEV1 was recorded at baseline and 2, 4, 6, 8, 10, and 12 h after drug administration; at the same times, with the exception of the 12th h, theophylline plasma concentrations were also measured. When compared to theophylline, bronchodilation induced by salmeterol was characterized by an earlier onset, a greater magnitude, and a longer duration. Given in combination with salmeterol, theophylline elicited a further slight increase in airway calibre with respect to the bronchodilator action of the β2-agonist alone, with FEV1 changes which resulted to be statistically significant at the 4th, 6th and 8th h after administration (p<0.05, p<0.03 and p<0.05, respectively). At the 4th h theophylline reached serum levels included within the therapeutic range, which were persistently maintained at least until the the 10th h. Therefore, our findings suggest that inhaled salmeterol and oral slow-release theophylline, the latter acting within the range of therapeutic plasma concentrations, exert additive bronchodilating effects in asthmatic patients with moderate to severe airflow limitation.