Bronchodilating Effects of Combined Therapy With Clinical Dosages of Ipratropium Bromide and Salbutamol for Stable COPD

Comparison With Ipratropium Bromide Alone

¹ From the Chest Disease Research Institute, Kyoto University, Kyoto, Japan

Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5±5.9 years; FEV₁, 0.87±0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 µg ipratropium bromide, (2) 80 µg ipratropium bromide, (3) 40 µg ipratropium bromide plus 200 µg salbutamol, (4) 80 µg ipratropium bromide plus 400 µg salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV₁ responses to combined dosages of 80 µg ipratropium bromide and 400 µg salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 µg salbutamol with 40 µg ipratropium bromide compared with 40 µg ipratropium bromide alone. Combination therapy with 200 µg salbutamol and 40 µg ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 µg ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 µg ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.

Key Words: bronchodilator • chronic obstructive pulmonary disease • ipratropium bromide • salbutamol

Submitted on November 8, 1993
Accepted on July 11, 1994

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