EFFECT OF 3 DIFFERENT DOSES OF A SLOW-RELEASE THEOPHYLLINE FORMULATION ON BRONCHIAL RESPONSE TO INHALED METHACHOLINE IN ASTHMATIC-PATIENTS

This study investigated whether or not a sustained release formulation of theophylline (SRT) at different dosages had any effect on bronchial hyperresponsiveness as measured by the methacholine challenge. On four separate occasions, 16 patients with mild asthma took either placebo or 300, 400, 500 mg of SRT twice a day. SRT had a slight bronchodilating effect that was not dose-related, but produced a dose-related decrease in the bronchial response to inhaled methacholine (r = 0.39, p = 0.007). This effect was present after all three treatment periods with the active drug when mean +/- SE theophylline serum concentrations of 10.3 +/- 0.7, 12.6 +/- 0.9 and 17.1 +/- 1.1 mg/l respectively were reached. A highly significant relationship between theophylline serum concentration and the degree of protection against methacholine bronchospasm was also found (r = 0.45, p = 0.001). It is concluded that oral theophylline does reduce bronchial hyperresponsiveness in a dose dependent fashion, this effect being present at all the serum concentrations within the normal range.