FORMOTEROL, A NEW INHALED BETA-2 ADRENERGIC AGONIST, HAS A LONGER BLOCKING EFFECT THAN ALBUTEROL ON HYPERVENTILATION-INDUCED BRONCHOCONSTRICTION

The duration of effect of inhaled formoterol (24 μg) was compared with that of a placebo and that of inhaled albuterol (200 μg) in 12 adult asthmatic subjects who underwent hyperventilation tests with cold dry air (-20°C) on 4 study days. On the control day, they were subjected to four hyperventilation tests to ensure functional stability. On the 3 remaining days, after a first hyperventilation test, they inhaled placebo, albuterol, or formoterol in randomized, double-blind fashion. The hyperventilation test was repeated 1, 4, and 8 h and, if the blocking effect was still present, 12 and 24 h after the drug had been administered. The dose of hyperventilation of cold air causing a 20% fall in FEV1 (PD20) was interpolated on the dose-response curve. The magnitude of the blocking effect at each time interval on each study day was assessed by comparing the changes in PD20 from baseline with the within-day variability of PD20 (standardized change in PD20). The acute bronchodilator effect was not significantly different as assessed 15 min (21 ± 14% for albuterol and 18 ± 18% for formoterol) and 1 h (20 ± 13% for albuterol and 18 ± 17% for formoterol) after administering the medication. The duration of the blocking effect, defined as the return to 2 SD from the standardized change in PD20, was significantly more prolonged for formoterol (8.0 ± 3.4h) than for albuterol (3.0 ± 1.7 h) (t = 4.2, p < 0.0001). Two subjects still demonstrated the presence of a blocking effect 4 h after inhaling albuterol, whereas 11 subjects did after formoterol. After 12 h, three subjects still demonstrated the presence of a blocking effect after inhaled formoterol. We conclude that the protection against bronchoconstriction induced by hyperventilation of unconditioned air in asthmatic subjects is significantly more prolonged after formoterol than after albuterol.