Dose-related efficacy and safety of formoterol (Oxis) Turbuhaler compared with salmeterol Diskhaler in children with asthma

Abstract

To compare the dose-related bronchodilator efficacy and tolerability of formoterol (Oxis) Turbuhaler with salmeterol Diskhaler and placebo in children with asthma. A single-dose, randomized, double-blind, incomplete crossover study of 68 children (7-17 years), with moderate-to-severe asthma, 82% receiving inhaled corticosteroids. Patients received four of six treatments [4.5, 9, 18, or 36 microg formoterol (6, 12, 24 or 48 microg metered doses), 50 microg salmeterol (metered dose) or placebo] at 12-h visits, separated by > or =3 days. Forced expiratory volume in 1 s (FEV1), pulse, blood pressure, electrocardiogram, adverse events and urine formoterol were assessed. The therapeutic ratio of formoterol vs. salmeterol was estimated from the efficacy and systemic effects results. All active treatments significantly improved FEV1 compared with placebo. Formoterol 9-36 microg provided dose-related increases over salmeterol in lung function: average 12-h FEV1 (increases of 4.9-8.7%, p < 0.001) and FEV1 at 12 h post-dose (7.0-12.2%, p < 0.001). The onset of effect of formoterol was also significantly faster than salmeterol for doses > or =9 microg. Salmeterol 50 microg was estimated to be equieffective to 3.3 microg formoterol for 12-h average FEV1 and the estimated equieffective dose for a variety of systemic effects was 7.8-13.5 microg formoterol. All treatments were well tolerated. Formoterol (Oxis) Turbuhaler 4.5-36 microg provided dose-related improvements in bronchodilator efficacy in children with asthma. Formoterol > or =9 microg provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 microg with no increase in systemic effects.