Serum theophylline and ventilatory function in chronic obstructive lung disease. Comparison between two slow-release formulations of theophylline.

Pharmacokinetics and ventilatory response to Theodur (Th) was compared to that of Aminomal R (AR) in a randomized within-patient double-blind study, carried out in patients with chronic obstructive lung disease. Both slow-release preparations of theophylline were given every 12 hours for 14 days each at the end of a placebo wash-out period. Th and AR did not differ significantly in their bronchodilating effect at 3 and 12 hours after intake. Salbutamol consumption was not dissimilar in the 2 preparations. Mean serum theophylline levels remained within the therapeutic range at 2, 3 and 12 hours after sustained administration of both Th and AR, but were slightly lower and less fluctuating after Th. Gastrointestinal side effects such as epigastric discomfort, nausea, abdominal pain and diarrhea were more common after AR, a result likely due to its higher content of anhydrous theophylline per tablet (474 mg vs 300 mg in Th). In conclusion, we failed to detect differences between Th and AR in their bronchodilating effect after sustained treatment in patients with chronic obstructive lung disease. Th, however, although containing less theophylline per tablet, resulted in comparable theophylline levels with similar ventilatory response, in presence of a better gastrointestinal tolerability. These results suggest a better bioavailability of Th, likely accounted for by a more advanced pharmaceutical technology.