THE EFFECT OF MAXIMAL DOSES OF FORMOTEROL AND SALBUTAMOL FROM A METERED DOSE INHALER ON PULSE RATES, ECG, AND SERUM POTASSIUM CONCENTRATIONS

In a randomized, double-blind, crossover cumulative study, the individual maximal bronchodilator dosages for formoterol (F) and salbutamol (S) were assessed for their respective influence on ECG, pulse rate, and serum potassium levels in 13 patients with stable and reversible asthma. The following dosages were administered with an interval of 1 h: 12-24-48-(48)-(48) mu-g for F and 100-200-400-400-(400)-(400) mu-g for S. The study day was discontinued if pulse rate was above 140 beats.min-1, a flattening of T wave on the ECG was recorded, or a maximal bronchodilation in FEV1 was observed (above 110 percent of the predicted value or an increase in FEV1 in the last two measurements below 5 percent). The maximal individual dose of F administered was 84-mu-g in six patients, 132-mu-g in three patients, 180-mu-g in three patients, and 228-mu-g in one patient. For S, the maximal individual dose was 400-mu-g in three patients, 2,200-mu-g in eight patients, 3,000-mu-g in one patient, and 3,800-mu-g in one patient. The mean maximal increase in FEV1 was 36.0 percent after F and 35.1 percent after S. Pulse rate increased from 73 to 83 beats.min-1 after F and from 75 to 84 beats.min-1 after S (both statistically significant). No pulse rate above 140 beats.min-1 was observed. In the high-therapeutic range (up to 36-mu-g of F and 6,090-mu-g of S), no changes in potassium level were observed. In still higher dosages, mean potassium level decreased from 4.16 to 3.78 mmol.L-1 after F and from 4.02 to 3.88 mmol.L-1 after S (not clinically relevant). The lowest individual potassium level recorded was 3.1 mmol.L-1. No clinically important changes in ECG were observed. In conclusion, very high doses of F and S administered from a metered dose inhaler proved to be safe for patients.