Acute Controlled Study of the Dose-Response Relationship of Fenoterol, Ipratropium Bromide and Their Combination

A double-blind study was carried out in a group of 9 patients with partially reversible airway obstruction, to evaluate the bronchodilator effect of gradually increased doses of fenoterol (cumulative doses: 100, 200, 400, 800 and 1,600 micrograms), ipratropium bromide (40, 80, 160, 320 and 640 micrograms) and a combination of these (100 + 40, 200 + 80 micrograms, etc.), denominated Duovent. The three treatments were carried out at random at the same time on 3 days, usually not consecutive days, whereby 1, 1, 2, 4 and 8 puffs (altogether 1, 2, 4, 8 and 16 doses) of each product were given in identical pressurized aerosols at intervals of 60 min. Respiratory (spirometry and flow-volume curve) and cardiovascular (blood pressure, heart rate) parameters were measured under basal conditions and 60 min after each administration. On average, with all three products, the bronchodilatory effect showed a linear correlation with the logarithm of the dose given. With the same number of puffs the side-effects (tremor in particular) of the combination fenoterol and ipratropium bromide or Duovent (FIB) were markedly fewer than those of fenoterol, while ipratropium bromide was very well tolerated. The three dose-response curves (parallel) show that, in respect of an increase in FEV1, 1 puff of Duovent (100 micrograms fenoterol + 40 micrograms ipratropium bromide) is approximately equal to 2 puffs of fenoterol (200 micrograms) and 4 puffs of ipratropium bromide (160 micrograms). FIB, therefore, makes it possible to maintain the same bronchodilatory effect as the full dose (400 micrograms) of fenoterol while improving the therapeutic value.