Bronchodilating effect of oral theophylline-ephedrine combination

Ten adults with mild but continuously symptomatic asthma were compared with 10 nonsmoking normal persons. In Phase I after 2 wk without oral bronchodilators and 8 hr without aerosols, each subject received on five different days and in a randomized sequence either placebo, ephedrine 24 mg, theophylline 130 mg, theophylline + ephedrine, or theophylline + ephedrine +phenobarbital 8 mg. During Phase II, the 20 subjects took the theophylline-ephedrine-phenobarbital compound 4 times a day for 2 wk and continued this schedule for an additional 10 to 14 days while the five drug administrations of Phase I were repeated. The drug effects were evaluated by spirometry and flow volume loops and correlated and blood levels of theophylline. A single dose of the combination produced therapeutically useful bronchodilation of central and peripheral airways without producing much more frequent or severe side effects than either drug alone. The greater improvement that occurred by combining a low dose of theophylline with a low dose of ephedrine does not preclude a conclusion that similar improvement could have been achieved with a larger dose of theophylline. Addition of phenobarbital did not reduce symptoms of nervousness, tremor, or nausea. After 2 wk or longer of repeated doses, the combination produced about as much bronchodilation as after a single dose. Before the second set of measurements, theophylline levels had reached steady state after regular administration of 130 mg four times a day. Eight hours after the single dose, the mean serum level was 2.3 μg/ml; after 2 wk of repeated doses, 8 hr after a dose the mean was 5.3 μg/ml. Each drug, and the combination more than either, had a bronchodilating effect on small airways of normal subjects.