Comparison of a New Sustained-Release Theophylline Formulation (Theotrim) with a Reference Drug (Theodur) in the Steady State in Asthmatic Children

Abstract

The bioequivalency of two sustained-release theophylline formulations (SRT), Theotrim and Theodur, was studied in the steady state in asthmatic children, using a double-blind crossover design. Ten children, aged 7–14 (mean 10.2) years, were treated for 2 weeks, with identical doses (mean 16 mg/kg•day) of either Theotrim or Theodur tablets. Each drug was given for 1 week in a randomized sequence. At the end of each week, a 12-hour serum theophylline concentration (STC) profile was performed and pharmacokinetic data of both drugs were compared. Peak STCs with Theotrim and Theodur were 17.1 ± 1.4 μg/ml (M ± SEM) and 16 ± 1 μg/ml (M ± SEM), respectively. Through STC were 8.9 ± 0.8 μg/ml (M ± SEM) with Theotrim compared with 9.4 ± 0.8 μg/ml (M ± SEM) with Theodur. Six patients had % fluctuation of STC < 100% with both Theotrim and Theodur, while the mean (±SEM) % fluctuation was 99(±17)% and 79(±15)% with Theotrim and Theodur, respectively. The area under the concentration curve (AUC) for 0–12 hours was 158.9 ± 13 (M ± SEM) μg/hr•ml for Theotrim, compared with 153.0 ± 10 (M ± SEM) μg/hr·ml for Theodur. The differences between all these pharmacokinetic parameters showed no statistical significance (p > 0.1). Likewise, there were no differences in the frequency of symptoms of asthma, requirement for additional bronchodilator medication, and theophylline side effects in the patients during the week of treatment with Theotrim compared with the other week when treated with Theodur. We conclude that in this group of asthmatic children, Theotrim proved to be bioequivalent to Theodur in the steady state and equally effective in the treatment of asthma.