The extrapulmonary effects of increasing doses of formoterol in patients with asthma

Abstract

Objective: To assess the cardiovascular and metabolic responses to increasing doses of formoterol administered from a dry powder inhaler. Methods: Twenty patients with mild to moderate asthma were given 12, 24, 48 and 96 μg of formoterol or a matched placebo on separate days. The doses were administered using a randomised, cross-over, double-blind design. The effects on heart rate, blood pressure, electromechanical systole (QS₂I), the electrocardiographic QTc interval, plasma potassium (K); blood glucose and FEV₁ were assessed prior to, and for 9 h following each dose. Results: There was no difference between the maximum effects of formoterol 12 μg and placebo; the 24 μg dose significantly decreased plasma K (−0.2 mmol · l⁻¹) and increased blood glucose (1.8 mmol · l⁻¹) compared to placebo. The two highest doses affected most of the variables with the 96 μg dose being significantly different from placebo for all indices, heart rate (9 beats · min⁻¹), systol BP (4 mmHg), diastolic BP (−3 mmHg), QS₂I (−11 ms), QTc (17 ms), plasma K (−0.5 mmol · l⁻¹) and blood glucose (2.6 mmol · l⁻¹). All doses of formoterol increased FEV₁. Conclusion: Although there were dose-dependent effects on the extrapulmonary measurements, only the effects at the highest dose may be of clinical significance.