Comparison of the bronchodilating effect of two doses of a sustained release theophylline

In order to assess the dose/response ratio of two different doses of theophylline, the effects of two periods of 4-day treatment with 300 and 450 mg sustained release anhydrous theophylline (Theodur, Astra, Sweden) b.i.d. in 16 in-patients with reversible chronic obstructive lung disease in a stable state were investigated in a double-blind randomized crossover study. On the 4th day in each treatment period, ventilatory function parameters (FEV1, FVC, PEFR, MEF25, MEF50), theophylline serum concentration and blood gases were measured. Asthma symptoms, beta 2-adrenergic aerosol use significantly different from its value before treatment: the mean FEV1 increase during the 300-mg period reached 12% and during the 450-mg period 15%. The mean difference in theophylline serum concentration between the periods of 300 and 450 mg reached approximately 2 micrograms/ml, but a significant difference could not be demonstrated between both treatment periods, neither in the mean ventilatory parameters, nor in the patients preference. In spite of the use of a sustained release preparation, variations of serum levels of theophylline were observed individually throughout a 12-hour observation period: the extent of those variations differs from one patient to another.