[Pharmacokinetics and pharmacodynamics of twice-daily unequal administration of theophylline retard pellets in children of various age groups].

To assess the pharmacokinetic parameters of theophylline (Euphylong as retard pellets) children were studied belonging to age groups between 9 to 13 and 5 to 9 years in twice-daily dosage with unequal distribution of the daily doses. For the older children the dose was 400 + 200 mg and for the younger ones 300 + 150 mg theophylline (these quantities represent the evening and morning doses). 16 and 14 children, respectively, completed the studies regularly. Pharmacokinetic evaluation resulted in a markedly parallel course of the individual serum theophylline profiles around the mean value. The average nocturnal concentration from 200 to 600 hours in the morning was higher than the average daytime concentration (11.4 to 10.5 mg/l or 12.3 to 11.4 mg/l). Due to the relatively stable baseline values the clinical parameters improved only slightly, but there were in particular significant changes in the peak-flow profile. In the older children we could also prove that they had a better protection against metacholine provocation. The side effects were generally mild and were in accordance with previous experiences collected with the studied preparation. The dosage scheme with unequal distribution of the total daily dose is recommended, on the basis of the present study, for all patients with rapid theophylline metabolism, i. e. children, habitually strong smokers or if the clearance is accelerated due to endogenous factors.