Slow-release terbutaline and theophylline for the long-term therapy of children with asthma: a Latin square and factorial study of drug effects and interactions

Abstract

To evaluate the long-term effects of slow-release formulations of theophylline and terbutaline on pulmonary function, clinical symptoms, and side effects, 24 children with stable and moderately severe perennial asthma participated in a prospective double-blind cross-over study. The patients and the treatments were randomized according to the Latin square design to eliminate all possible period/climate biases throughout the protracted study period. The treatments consisted of terbutaline, 5 mg, theophylline, 200 mg, the combination, and placebo, given twice daily orally and crossing over every 28 days. The two drugs, administered alone or in combination, improved lung function and symptoms when compared with placebo. The interaction of theophylline and terbutaline was quantitatively shown by 2 x 2 factorial statistical design to be essentially additive rather than synergistic in the control of asthma. No increase in side effects was noted when the combined therapy was used. These findings suggest therapeutic advantages to combining submaximal oral doses of sustained-release theophylline and terbutaline for the long-term treatment of children with asthma.