Comparison of the Bronchodilating Effect of Two Doses of a Sustained Release Theophylline

Abstract

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 (FEVi, FVC, PEFR, MEF25, MEF₅₀), theophylline serum concentration and blood gases were measured. Asthma symptoms, β₂-adrenergic aerosol use and side effects were recorded daily. The mean FEV₁ during both treatment periods was 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 μg/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