Dose-related efficacy and safety of formoterol (Oxis (R)) Turbuhaler (R) compared with salmeterol Diskhaler (R) in children with asthma
Abstract
To compare the dose-related bronchodilator efficacy and tolerability of formoterol (Oxis(R)) Turbuhaler(R) with salmeterol Diskhaler(R) 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 mug formoterol (6, 12, 24 or 48 mug metered doses), 50 mug salmeterol (metered dose) or placebo] at 12-h visits, separated by greater than or equal to3 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 mug 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 greater than or equal to9 mug.
Salmeterol 50 mug was estimated to be equieffective to 3.3 mug formoterol for 12-h average FEV1 and the estimated equieffective dose for a variety of systemic effects was 7.8-13.5 mug formoterol. All treatments were well tolerated.
Formoterol (Oxis) Turbuhaler 4.5-36 mug provided dose-related improvements in bronchodilator efficacy in children with asthma. Formoterol greater than or equal to9 mug provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 mug with no increase in systemic effects.