ORAL DOXOPHYLLINE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

Doxophylline, or 2-(7'-theophyllinemethyl)1,3-dioxolane, is a theophyl line derivative which has shown interesting bronchodilating activity, and it appears to determine few adverse effects. The aim of the presen t investigation was to evaluate clinical therapeutic effects of the dr ug in the treatment of 2 groups of patients suffering from moderate to severe chronic obstructive pulmonary disease differing in acute respo nse to the inhaled beta(2)-agonist salbutamol and to compare changes o f lung function tests to serum concentration of doxophylline. We studi ed 67 patients with chronic obstructive pulmonary disease (median age 63 years, 9 females and 58 males) who were all clinically stable at th e time of the study. Patients were separated into 2 groups on the basi s of their reaction to inhalation of 200 mu g of salbutamol: those wit h an increased FEV(1) of more than 20% from baseline value (group 1), and those with no increase (group 2). Doxophylline was administered or ally at the dose of 400 mg 3 times daily. Serum levels of doxophylline were determined by high-pressure liquid chromatography. Spirometry an d blood gas analysis were performed before and 10 days after treatment . Four patients stopped drug assumption because of side effects (3 for dyspepsia and 1 for anxiety). In group 1 (34 patients), a significant increase in SVC, FVC, FEV(1),FEF 25 - 75% and PEFR was observed. In g roup 2 (29 patients), only PEFR significantly increased. No modificati ons in blood gas analysis were observed. The mean serum level of doxop hylline was 14 mu g/ml in group 1 and 9 mu g/ml in group 2: the differ ence was statistically significant. The relation between serum levels of doxophylline and FVC showed an increase in the parameter up to the concentration of 12 - 13 mu g/ml, after which a plateau phase was obse rved. On the basis of our data, doxophylline appears to have an intere sting bronchodilating effect in patients responsive to the inhaled bet a(2)-agonist salbutamol. The lower limit of the therapeutic range seem s to be 12 - 13 mu g/ml. The upper limit of the therapeutic range was not determined because it was not possible to obtain serum samples whe n side effects occurred.