THERAPEUTIC EQUIVALENCE OF A GENERIC SLOW-RELEASE THEOPHYLLINE TABLET

Study Objective. To evaluate the relative bioavailability and clinical efficacy of two slow-release theophylline products. Design. Randomize d, double-blind, crossover trial. Setting. A university-affiliated cli nical research center. Patients. Fourteen adults with asthma. Interven tions. The patients received a generic slow-release theophylline table t or Theo-Dur at bedtime for 5 nights. Measurements and Main Results. Serum drug concentrations were measured after the last dose. Attenuati on of exercise-induced bronchospasm (EIB) was included as a surrogate for efficacy. There was no significant difference in extent of absorpt ion. The mean differences between the generic product and Theo-Dur in area under the curve was -13.9 mu g/ml.hr(-1) (95% CI -41 to 12.9, p=0 .3) and in peak concentration (C-max), -0.5 mu g/ml (95% CI -1.7 to 2. 7, p=0.6). In contrast, the generic product was absorbed more rapidly; the mean differences in the time to peak concentration (T-max) was -3 .0 hours (95% CI -4.3 to -1.7, p=0.0003), in trough concentration (C-m in), -0.9 mu g/ml(95% CI -1.9 to -0.01, p=0.05), and in fluctuation be tween C-max and C-min, +128% (95% CI 40 to 217, p=0.008). Neither prod uct effectively attenuated EIB, since mean serum concentrations during the exercise challenges were unexpectedly below 10 mu g/ml after both products. Conclusion. These two products are not bioequivalent, but t he difference in absorption rates is unlikely to be clinically importa nt in most patients (i.e., they are therapeutic equivalents).