Reducing adverse effects of inhaled fenoterol through optimization of the aerosol formulation.

Abstract

We compared the adverse effects of 160 micrograms of fenoterol in the form of a 2.8-micron monodisperse aerosol with those of 800 micrograms of fenoterol as a conventional metered dose inhaler (MDI) aerosol plus spacer. Previously, a monodisperse aerosol was shown to elicit equivalent degrees of bronchodilation at an 80% lower dose using a standard MDI. A total of 12 healthy volunteers (8 women and 4 men) participated in this study and inhaled in random order a placebo, the monodisperse aerosol, and the MDI aerosol. Changes in serum potassium level, finger tremor, blood pressure, heart rate, and specific airway conductance were measured before and 15 minutes after administration. Compared with placebo, the active aerosols elicited a significant improvement in airway conductance and adverse effects. Serum potassium level decreased by 0.27 mmol/L after the monodisperse aerosol, and the MDI lowered it by 0.67 mmol/L (P = 0.001). Finger tremor also increased less: 0.07 versus 0.29 V (P = 0.029). Changes in cardiovascular parameters were not significantly different from those elicited by the placebo. There were no significant specific airway conductance differences between the two active aerosols. By changing the formulation of MDI aerosols, the occurrence of adverse effects can be reduced.