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The consistency of theophylline absorption from a sustained-release formulation in asthmatic children
M Hill1, J R Haltom, S J Szefler
1Department of Pediatrics and Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Insights
Sustained-release theophylline (Slo-Bid) showed complete absorption in asthmatic children, but with higher than desired fluctuations. Absorption time varied between morning and evening doses, suggesting potential for dose adjustments in pediatric asthma management.
Area of Science:
- Pharmacokinetics
- Pediatric Pulmonology
- Drug Delivery Systems
Background:
- Asthma management in children requires optimal theophylline dosing.
- Sustained-release formulations aim to maintain therapeutic serum theophylline concentrations (STCs).
- Understanding absorption variability is crucial for effective pediatric therapy.
Purpose of the Study:
- To evaluate the absorption and pharmacokinetic profile of sustained-release theophylline (Slo-Bid) in asthmatic children.
- To assess the consistency of absorption and identify factors influencing serum theophylline concentrations.
- To compare absorption times between morning and evening doses.
Main Methods:
- Administered Slo-Bid to asthmatic children (ages 2-7) twice daily for 7-day intervals.
- Monitored serum theophylline concentrations (STCs) every 2 hours for 24 hours post-administration.
- Calculated absorption, elimination, and mean residence times, including time for absorption (ta).
Main Results:
- Slo-Bid demonstrated complete absorption (104.8-117.1%) with consistent daily patterns.
- Maximum STCs occurred 2-6 hours post-dose; minimums near the evening dose.
- Percentage of fluctuation was higher than desired (149.7-163.0%), likely due to rapid theophylline clearance (119.9 ml/hr/kg).
- Mean residence time for absorption (ta) was significantly longer after PM doses (3.7-3.9 hours) compared to AM doses (2.7-2.8 hours) (p < 0.0001).
Conclusions:
- Sustained-release theophylline is well-absorbed in young asthmatic children.
- Higher than ideal fluctuations in STCs may be linked to rapid theophylline clearance in this population.
- Significant differences in absorption time between AM and PM doses warrant consideration for optimizing dosing regimens in pediatric asthma.
Abstract:
Theophylline absorption was studied in asthmatic children ages 2-7 years. A bead-filled capsule of sustained-release theophylline (Slo-Bid, William H. Rorer, Inc., Fort Washington, PA) was administered in equal doses twice daily (8 AM and 8 PM) to produce serum theophylline concentrations (STCs) between 10 and 20 micrograms ml. After 7 days, blood samples were obtained every 2 hours for 24 hours. This sequence was repeated after another seven days of treatment. Elimination values were calculated after an intravenous reference dose. Slo-Bid was completely absorbed (mean +/- SD percentage of dose absorbed of 117.1 +/- 26.1 on day 1, and 104.8 +/- 16.1% on day 2), and the pattern of absorption was consistent from day to day, with maximum STCs occurring 2-6 hours after the dose, and minimum STCs at or near the time of PM dose. The percentage of fluctuation of 149.7 +/- 49.7% and 163.0 +/- 114.0% (mean +/- SD) on days 1 and 2, respectively, was slightly higher than desired, but probably was a result of rapid theophylline clearance in this group of children (119.9 +/- 25.8 ml/hr/kg). Mean residence time for absorption after AM and PM doses indicated significantly longer time for absorption (ta) after the PM doses: mean +/- SEM ta for AM doses on days 1 and 2 was 2.8 +/- 0.3 and 2.7 +/- 0.2 hours, respectively, and increased to 3.9 +/- 0.3 and 3.7 +/- 0.5 hours after PM doses on days 1 and 2, respectively (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)