Tolerability of high cumulative doses of the HFA modulite beclomethasone dipropionate/formoterol combination inhaler in asthmatic patients

The corticosteroid beclomethasone dipropionate (BDP) has been formulated with the long acting beta agonist formoterol (BDP/formoterol 100 μg/6 μg, Foster™) in a single inhaler using Modulite® technology. We have investigated the acute tolerability of high, cumulative doses of BDP/formoterol compared to formoterol alone and placebo. This was a double blind, 3-way cross-over comparison of 10 puffs of BDP/formoterol 100 μg/6 μg or formoterol 6 μg or placebo during maintenance treatment with BDP/formoterol two puffs per day. Pharmacokinetics over 12 h during maintenance treatment was measured on day 7. High cumulative doses were then administered on three separated days. Eighteen patients with asthma were recruited (mean FEV1 65% predicted). The primary endpoint was serum potassium over the 12 h period after high doses. QTc, blood pressure and heart rate over 12 h, and plasma lactate and glucose over 3 h following dosing were assessed. Formoterol caused a significantly greater decrease in serum potassium than BDP/formoterol or placebo (difference in mean minimum concentrations; 0.11 and -0.15 mmol/l, respectively, p