H2-antagonist derangement of the kinetics of sustained-release oral theophylline.

: The authors have evaluated the interference of the H2-antagonists cimetidine and ranitidine with the elimination kinetics of sustained-release anhydrous theophylline, administered per os at the dose of 300 mg b.i.d. in two randomly selected groups of patients suffering from chronic obstructive lung disease. The plasma theophylline trends (obtained over a 12-hour period) were compared in the two groups in basal conditions (on reaching the theophylline steady state) and after 8 days treatment with cimetidine or ranitidine. In addition, the bronchodilator effect of theophylline was evaluated in these experimental conditions by means of FEV1 measurements. Simultaneous administration of ranitidine produced no changes in theophylline elimination, and the bronchodilator effect of theophylline proved both substantial and systematic in the patients treated with this H2-antagonist. On the other hand, the patients treated with cimetidine showed a marked, systematic increase in theophylline plasma levels, even exceeding the upper limit of its known therapeutic range in 4 cases. Despite this, no evidence of a bronchodilator effect was found in the cimetidine-treated patients, while significant effects attributable to theophylline toxicity were observed in the 4 cases with excessive theophylline plasma levels. The simultaneous administration of cimetidine in patients treated with sustained-release anhydrous theophylline thus proved capable of seriously undermining the strategy of theophylline usage precisely on account of the high degree of bioavailability of theophylline in the sustained-release formulation.