Objective: To determine whether a generic slow-release theophylline tablet (manufactured by Sidmak Laboratories, Inc.) is therapeutically equivalent to a proprietary theophylline tablet, Theo-Dur, in children.
Design: Prospective, randomized, double-blind, crossover trial.
Setting: Multicenter clinics.
Patients: 38 children, 6 to 16 years of age, with asthma.
Interventions: Individualized doses of Theo-Dur or generic tablet every 12 hours for 5 days.
Measurements and main results: During the last 24 hours of each regimen, theophylline serum concentrations were measured serially and a standardized exercise stress test was performed at 24 hours (trough serum concentration). Neither formulation effectively blocked the response to exercise; the maximum decrease in forced expiratory volume in the first second was 26.1% +/- 18.9% with Theo-Dur and 24.8% +/- 19.7% with the generic product (p = 0.68; beta = 0.08). The mean +/- SD peak serum concentrations were 18.0 +/- 3.0 micrograms/ml with Theo-Dur and 18.7 +/- 3.7 micrograms/ml with the generic tablet; the trough serum concentration was < 10 micrograms/ml in 15 subjects after administration of Theo-Dur and in 20 subjects after administration of the generic product. There were no significant differences in relative extent of absorption or the time to reach peak serum concentration.
Conclusions: This generic formulation and Theo-Dur are bioequivalent in children. However, these results cannot be extrapolated to slow-release theophylline formulations that have not been approved by the U.S. Food and Drug Administration as equivalent to Theo-Dur.