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

To assess the cardiovascular and metabolic responses to increasing doses of formoterol administered from a dry powder inhaler.

Twenty patients with mild to moderate asthma were given 12, 24, 48 and 96 microg 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.

There was no difference between the maximum effects of formoterol 12 microg and placebo; the 24 microg dose significantly decreased plasma K (-0.2 mmol x l(-1)) and increased blood glucose (1.8 mmol x l(-1)) compared to placebo. The two highest doses affected most of the variables with the 96 microg dose being significantly different from placebo for all indices, heart rate (9 beats x min(-1)), systol BP (4 mmHg), diastolic BP (-3 mmHg), QS2I (-11 ms), QTc (17 ms), plasma K (-0.5 mmol x l(-1)) and blood glucose (2.6 mmol x l(-1)). All doses of formoterol increased FEV1.

Although there were dose-dependent effects on the extrapulmonary measurements, only the effects at the highest dose may be of clinical significance.