Clinical relevance of theophylline chronokinetics for asthmatic children

In two studies, 25 diurnally active patients (6-17 years of age) were evaluated for day-night differences in serum theophylline concentration (STC) by frequent blood sampling over two consecutive 12-hr dosing intervals while being treated with Theo-Dur. In both studies, findings were similar; Cmax was greater and Tmax shorter following dosing at 0700 or 0800 vs. 1900 or 2000 with Cmax -Cmin approximately 7 micrograms/ml over the 24 hr. After the morning dosing, 22 of 25 patients exhibited Cmax within 4 hr; 23 of 25 exhibited Cmin 12 hr after this dosing. After the evening ingestion, the situation was very different: Cmin occurred within the initial 4 hr in 21 of 25 patients, whereas Cmax occurred in 22 of 25 patients just prior to the next (morning) dose. The findings indicate the most appropriate time to estimate Cmax in Theo-Dur-treated children is within the 4 hr after the morning ingestion. The best time to estimate Cmin is a few hours after the evening ingestion. Sampling at these times is likely to represent within 10-20% the actual Cmax or Cmin.