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Day-night differences in steady-state theophylline pharmacokinetics in asthmatic children
P H Scott1, W G Kramer, M H Smolensky
1Department of Pediatrics, Pathology and Pharmacy, Indiana University School of Medicine, Indianapolis.
Insights
Asthmatic children absorb theophylline more effectively during the day than at night. This study found no circadian rhythm in theophylline clearance, indicating absorption, not metabolism, varies with time of day.
Area of Science:
- Pharmacology
- Chronobiology
- Pediatric Asthma
Background:
- Theophylline is a bronchodilator used to treat asthma.
- Circadian rhythms can influence drug absorption and disposition.
- Understanding day-night differences in theophylline pharmacokinetics is crucial for optimizing treatment in pediatric asthma.
Purpose of the Study:
- To investigate potential day-night differences in the absorption and disposition of oral theophylline in asthmatic children.
- To determine if theophylline clearance exhibits a circadian rhythm.
Main Methods:
- A randomized crossover study design was used in day-active asthmatic children.
- Theophylline was administered orally as TheoDur tablets and Somophyllin-CRT capsules every 12 hours (0700 and 1900).
- Serum theophylline concentrations were also monitored during a continuous intravenous aminophylline infusion to assess baseline clearance.
Main Results:
- Theophylline clearance showed no significant day-night variation, remaining constant during intravenous infusion.
- Oral administration of both TheoDur and Somophyllin-CRT resulted in greater area under the serum concentration-time curve (AUC) during daytime dosing compared to nighttime dosing.
- Theophylline absorption was more rapid during the day, indicated by an earlier time to maximum concentration.
Conclusions:
- Theophylline clearance in asthmatic children does not appear to be influenced by a circadian rhythm.
- Absorption of theophylline from both TheoDur and Somophyllin-CRT is more rapid and complete during the day than at night.
- These findings suggest that the timing of oral theophylline administration may impact its efficacy in pediatric asthma patients.
Abstract:
Potential day-night differences of theophylline absorption and disposition were examined in day-active asthmatic children. Theophylline was given orally as TheoDur tablets and Somophyllin-CRT capsules (random crossover) every 12 hr (0700 and 1900), and patients were studied during two consecutive dosing intervals. In addition, patients were studied during the last 24 hr of a 48-hr continuous, intravenous aminophylline infusion. Serum theophylline concentrations were essentially constant during the intravenous infusion for the day and night periods. Thus, day and night clearances were nearly identical. Following oral administration of Somophyllin-CRT or TheoDur, areas under the serum concentration-time curves were greater during the day than the night, with Somophyllin-CRT yielding greater areas than TheoDur for both dosing intervals. Theophylline was absorbed more rapidly during the day than the night, as evidenced by a time to maximum concentration that occurred earlier in the daytime dosing interval. We conclude that theophylline clearance is not characterized by a circadian rhythm and that absorption of theophylline from Somophyllin-CRT and TheoDur is more rapid and complete during the day than the night.