BIOEQUIVALENCE OF A GENERIC SLOW-RELEASE THEOPHYLLINE TABLET IN CHILDREN

Objective: To determine whether a generic slow-release theophylline ta blet (manufactured by Sidmak Laboratories, Inc.) is therapeutically eq uivalent to a proprietary theophylline tablet, Theo-Dur, in children. Design: Prospective, randomized, double-blind, crossover trial. Settin g: Multicenter clinics. Patients: 38 children, 6 to 16 years of age, w ith asthma. Interventions: Individualized doses of Theo-Dur or generic tablet every 12 hours for 5 days. Measurements and main results: Duri ng the last 24 hours of each regimen, theophylline serum concentration s were measured serially and a standardized exercise stress test was p erformed 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 = 0.008). The mean +/- SD peak serum concentrations were 18.0 +/- 3.0 mu g/ml with Theo-Dur and 18.7 +/- 3.7 mu g/ml with the generic table t; the trough serum concentration was <10 mu g/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 relativ e extent of absorption or the time to reach peak serum concentration. Conclusions: This generic formulation and Theo-Dur are bioequivalent i n children. However, these results cannot be extrapolated to slow-rele ase theophylline formulations that have not been approved by the U.S. Food and Drug Administration as equivalent to Theo-Dur.