Two separate studies were conducted to evaluate the efficacy and safety of tulobuterol and the development of tachyphylaxis, if any, after prolonged use. The first, a double blind, crossover study, compared the efficacy and safety of tulobuterol aerosol 400 µg tid and salbutamol aerosol 200 µg tid in 38 patients with reversible obstructive airways disease. Each study period lasted 4 weeks, separated by a one week washout period. Evaluation of efficacy was performed on day 1 by monitoring spirometric values up to 6 hours postdosing. Additionally, changes in baseline pulmonary function were evaluated by measuring FEV1, FVC and PEFR at each weekly visit. Twenty-nine patients were evaluable. Tulobuterol was shown to be as effective as salbutamol in onset, peak, and duration of response. Mean increases in FEV1 after tulobuterol ranged from 22% at 5 minutes postdose to 30% at 1 hour postdose; a clinically significant mean increase of 24% was recorded after 3 hours. In comparison, mean increases for salbutamol were 24% at 5 minutes postdose and 31% at 1 hour postdose; after 3 hours the mean increase was 21%. Statistically significantly greater increases in mean baseline FEV1 were recorded in favor of tulobuterol. Following 2 weeks of each treatment, tulobuterol showed a mean increase of 14%, compared to a mean postsalbutamol increase of 12%. After 4 weeks, differences were again statistically significant, with tulobuterol showing a mean increase in baseline FEV1 of 17% compared to 3% for salbutamol. Tulobuterol treatment was associated with smaller changes in blood pressure and pulse rate than salbutamol. Furthermore, it was associated with fewer side effects, and both the investigator and the patients favored tulobuterol in their global evaluations. In a second, separate long-term open study, 64 patients with reversible airways obstruction were treated with tulobuterol metered dose (400 µg qid) inhaler. Monthly spirometric evaluations demonstrated a continually increasing predose FEV1 of up to 11.5% in one study group (N = 45; treated for 6 months) and up to 17.8% in a second group (N = 15; treated for an additional 6 months). In addition to improved baseline pulmonary function, postdose responses were significantly elevated. Measurements taken up to 6 hours post-tulobuterol at the final study visit were similar to those obtained at the start of the study and indicated that tachyphylaxis did not develop. Diary data showed improvement in daily PEFR and a significant reduction in pulmonary symptoms, with the number of symptom-free days tending to increase throughout the study. Although most patients were taking concomitant medication such as theophylline and beclomethasone, side effects were noted in only 4 patients, and cardiovascular parameters were minimally affected. Global assessment at the end of the study indicated that 60–70% of the patients showed improvement. © 1990, Springer-Verlag New York, Inc.. All rights reserved.
