Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to oxitropium bromide in chronic obstructive pulmonary disease

Background-An earlier study documented that, in patients with chronic obstr uctive pulmonary disease (COPD), addition of ipratropium bromide at the cli nically recommended dose (40 mu g) does not produce any further bronchodila tion than that achieved with salmeterol 50 mu g alone. However, the dose of ipratropium bromide needed to produce near maximal bronchodilation is seve ral times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be e stablished using doses higher than those currently recommended in the marke ting of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on th e single dose salmeterol induced bronchodilation in patients with stable an d partially reversible COPD. Methods-Thirty two outpatients received 50 pg salmeterol or placebo. Two ho urs after inhalation a dose-response curve to inhaled oxitropium bromide (1 00 mu g/puff) or placebo was constructed using one puff, one puff, two puff s, and two puffs-that is, a total cumulative dose of 600 mu g oxitropium br omide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients r eceived one of the following: (1) 50 pg salmeterol + 600 pg oxitropium brom ide; (2) 50 pg salmeterol + placebo; (3) placebo + 600 pg oxitropium bromid e; (4) placebo + placebo. Results-Salmeterol induced a good bronchodilation (mean increase 0.272 1; 9 5% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide el icited an evident dose-dependent increase in forced expiratory volume in on e second (FEV1) and this occurred also after pretreatment with salmeterol w ith a further mean maximum increase of 0.152 1 (95% CI of differences 0.124 to 0.180). Conclusions-This study shows that acute pretreatment with 50 pg salmeterol does not block the possibility of inducing more bronchodilation with an ant icholinergic agent when a higher than normal dosage of the muscarinic antag onist is used.