Prolonged Protection against Methacholine-induced Bronchoconstriction by the Inhaled β2-Agonist Formoterol
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Formoterol fumarate is a new, high-affinity, beta 2-adrenergic receptor agonist that causes bronchodilation for at least 12 h. The purpose of this study was to compare the magnitude and duration of the effect of inhalation of formoterol (12 and 24 micrograms), albuterol (200 micrograms), and placebo in terms of protection against methacholine-induced bronchoconstriction. The 16 stable adult asthmatic subjects were studied on four separate study days. On each study day the subjects inhaled 2 puffs of the study medication, and methacholine tests were performed at 30 min and 4, 8, and 12 h later. Results were expressed as the provocative concentration of methacholine required to cause a 20% fall in FEV1 (PC20). At 30 min, 12 and 24 micrograms formoterol caused a mean 14- to 20-fold decrease in responsiveness, and albuterol a 12-fold decrease. However, albuterol had no significant protective effect at 4 h or thereafter, whereas there was still an 8-fold decrease in responsiveness for 24 micrograms formoterol and a 6-fold decrease for 12 micrograms formoterol at 12 h. This study has shown that both doses of formoterol were still actively protective against induced bronchoconstriction 12 h after inhalation, with minimal side effects. This suggests that formoterol may prove to be a very useful bronchodilator for the treatment of patients with asthma who have significant airway hyperresponsiveness or nocturnal symptoms and who require inhaled beta 2-agonists at least twice daily.
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