Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to oxitropium bromide in chronic obstructive pulmonary disease
M. Cazzola et al., Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to oxitropium bromide in chronic obstructive pulmonary disease, THORAX, 54(12), 1999, pp. 1083-1086
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.