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

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 mu g 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 (QS(2)I), 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 mu g and placebo; the 24 mu g 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 mu g dose being significantly different from placebo for all indices, heart rate (9 beats.min(-1)), systol BP (4 mmHg), diastolic BP (-3 mmHg), QS(2)I(-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.