[Pharmacokinetics and chronotherapy of delayed action theophylline (Euphyllin CR)]

Monitoring of theophyllinaemia in the course of 24 h during treatment with theophylline anhydrate capsules (Euphyllin CR) was used in 20 children (9-15 years) and in 20 adults (18-61 years) with bronchial asthma. The doses used in children were 5.96 mg/kg at 7 a.m. and 10.2 mg/kg at 7 p.m., while in adults the morning and evening doses were similar (4.35 and 4.89 mg/kg). After the first dose in the morning the serum theophylline concentration (STC) did not differ in children and adults (10.4 and 10.5 mg/l). In adults the half-time of absorption was twice as high as in children (0.63 and 0.3 h), as well as the time when the peak theophylline concentration was reached (2.7 and 1.39 h). In children a double dose of the drug at night ensured a STC of 11.2 mg/l and a maximum theophyllinaemia (C max = 13.5 mg/l between 8 p.m. and 6 a.m. (measured by the EMIT method). In adults the values during the night were significantly lower than in day-time (STC: ANOVA test P less than 0.05, C max: T-test P less than 0.01). The percentage fluctuation in individual subjects was small (36-49) interindividual, fluctuations in children and adults were considerable (105 to 207). From the chronoprofile of the pharmacokinetics of Euphyllin CR ensues that at the age of 9-15 years the most important indicators are similar to those in adults and that both groups should be given at night a double dose, as compared with that administered in the morning.