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Bioequivalence of a generic slow-release theophylline tablet in children
S Kanthawatana1, R C Ahrens, M McCubbin
1College of Pharmacy, University of Florida, Gainesville.
Insights
This study found a generic slow-release theophylline tablet to be bioequivalent to Theo-Dur in children with asthma. However, the findings do not apply to unapproved generic theophylline formulations.
Area of Science:
- Pharmacology
- Pediatric Asthma Management
Background:
- Asthma is a common chronic respiratory disease in children.
- Theophylline is a bronchodilator used in asthma management.
- Evaluating the bioequivalence of generic versus proprietary formulations is crucial for therapeutic interchange.
Purpose of the Study:
- To assess the therapeutic equivalence of a generic slow-release theophylline tablet (Sidmak Laboratories, Inc.) compared to Theo-Dur in pediatric patients.
- To determine if the generic formulation provides comparable theophylline serum concentrations and clinical effects.
Main Methods:
- A prospective, randomized, double-blind, crossover trial was conducted.
- 38 children (6-16 years) with asthma participated across multicenter clinics.
- Patients received individualized doses of either Theo-Dur or the generic tablet every 12 hours for 5 days.
Main Results:
- No significant differences were observed in theophylline serum concentrations or time to peak concentration between the two formulations.
- Both formulations showed limited efficacy in blocking exercise-induced bronchoconstriction.
- Peak serum concentrations averaged 18.0 mcg/ml for Theo-Dur and 18.7 mcg/ml for the generic tablet.
Conclusions:
- The generic slow-release theophylline tablet is bioequivalent to Theo-Dur in children.
- These findings support the use of this specific generic formulation as an alternative to Theo-Dur.
- Results should not be generalized to other unapproved slow-release theophylline products.
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.