Formoterol fumarate, a new beta 2-adrenoceptor agonist. Acute studies of selectivity and duration of effect after inhaled and oral administration

Abstract

Four double-blind, double-dummy, randomized, crossover studies were performed in nine asthmatic patients to evaluate beta 2-adrenoceptor selectivity and the duration of effect of formoterol. One study with cumulatively increasing doses of formoterol and salbutamol showed that with the inhaled route, formoterol was 5-15 times more potent than salbutamol with respect to bronchodilation. In a second study, 6 micrograms formoterol and 0.1 mg salbutamol were given for comparison of effect duration. Five hours after salbutamol inhalation the FEV1 values were back to basal. Eight hours after formoterol inhalation about 75% of the maximum bronchodilation remained and the FEV1 was significantly higher than after salbutamol inhalation. By oral route, a study with cumulatively increasing doses showed that as a bronchodilator formoterol was about 50 times more potent than salbutamol. The same potency difference was seen for increase of heart rate and decrease of diastolic blood pressure, indicating that the clinical selectivity for beta 2-adrenoceptors is equal for the two drugs. In a fourth study comparable doses by oral route did not show any difference in the duration of bronchodilation. We conclude that inhaled formoterol is 5-15 times more potent than salbutamol. Inhaled formoterol produces longer duration of bronchodilation, with clinically relevant bronchodilation for at least 8 h. The prolonged duration of formoterol was not seen with oral treatment.