Safety and efficacy of once-daily Uniphyl tablets compared with twice-daily Theo-Dur tablets in elderly patients with chronic airflow obstruction.
Oxygen desaturation and subclinical coronary artery disease may predispose older patients with chronic airflow obstruction to cardiac arrhythmias, especially when high concentrations of theophylline are present in the blood. To assess the safety and efficacy of Uniphyl tablets, an oral theophylline preparation formulated for once-daily dosing, in elderly patients with chronic airflow obstruction, we conducted a randomized, three-phase, double-blind crossover study comparing evening dosing with Uniphyl tablets, Theo-Dur tablets administered twice daily, and placebo. The patients in the study were scheduled to receive each treatment for two weeks. Each day, symptoms, side effects, peak expiratory flow rates, and use of metered-dose inhalers were recorded. Near the end of each phase, serum theophylline concentrations were measured every two hours between 8:00 A.M. and 8:00 P.M. on two consecutive days. The patients underwent ambulatory Holter monitoring during the final 48 hours of each phase. Twelve patients completed the active-drug phases of the study, but seven of the 12 were removed from the placebo phase because of increasing symptom severity. The difference between the number of patients completing the active-drug and placebo phases was statistically significant (p less than 0.001). Treatment with Uniphyl tablets resulted in a significantly (p less than 0.05) greater increase in peak expiratory flow rate than Theo-Dur tablet therapy, and both active drugs increased peak expiratory flow rate more than placebo. Circadian variation in peak expiratory flow rate was seen during the placebo and Theo-Dur tablet phases but not during the Uniphyl tablet phase. Symptoms and side effects were similar during the two active-drug phases. Cardiac ectopy was observed in most of the patients, but it was not significantly greater during the theophylline phases than during the placebo phase. Furthermore, ectopic activity was not directly related to the times of maximal serum theophylline concentration.
D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011897:Random Allocation; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D013607:Tablets; D013806:Theophylline