Pharmacokinetics and dose regimen of oral theophylline in children.

The pharmacokinetics of theophylline after oral administration in tablet (Oxyphyllin) or solution (Teovent) form was determined in 22 children 0.6-16 years of age. Four of these children also received intravenous theophylline. The absorption of theophylline both from the tablets and from the solution was rapid (mean half-time 14.3 and 16.1 min., respectively) and almost complete. The youngest children (2-8 years) given tablets had a significantly shorter half-time of elimination and a higher total plasma clearance than children aged 9-16 years. Adverse effects during treatment with the oral solution were studied in another 19 children. Medication was stopped by the parents of two children because of the unpleasant taste. Gastrointestinal disturbances were frequent but not serious enough to cause discontinuation of treatment. Simulations based on obtained pharmacokinetic data showed that in the average child below nine years of age oral theophylline, 6-8 mg/kg three times daily, would give plasma levels between 10 and 20 micrograms/ml (55-110 mumol/l) for about 60-70% of the day. A dose of 6 mg/kg four times daily would achieve such concentrations during almost 24 hrs of the day. In the average child aged 9-16 years a reduced dose of about 5-6 mg/kg three times daily would suffice to produce plasma levels of 10-20 micrograms/ml owing to the slower elimination of the drug in this age group. Individual titration of the dose is necessary for optimal treatment with theophylline in all age groups.

Pharmacokinetics of theophylline in young children with asthma: comparison of rectal enema and suppositories.

Six children, aged 2 months - 4 years, received theophylline 5-6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t 1/2 beta) was 3.75 h, i.e., shorter than in adults, but there was a considerable interindividual variation (1.8-7.0 h, in one patient 13.3 h). Thirteen children (2 months - 4 years) received theophylline suppositories in a dose of 3.8-5.0 mg/kg, and ten (6 months - 4 years) in a dose of 8.4-14.5 mg/kg. Absorption was slow (mean half-time 43 min), incomplete and variable (biological availability 8-100%, mean 80%). Only four of the patients given the higher dose and none given the lower dose reached a therapeutic serum concentration (10-20 microgram/ml). Nine children (6 months - 4 years) received rectal enemas of theophylline 4.1-9.2 mg/kg. Absorbtion was rapid (mean half-time 5.5 min) and biological availability averaged 100%. Six patients reached a serum concentration within the therapeutic range. Using the mean values of the calculated pharmacokinetic parameters, rectal enemas providing a dose of theophylline of 6-8 mg/kg t.i.d. were computed to give serum concentrations between 8-20 microgram/ml, without producing too high a level during the absorption phase.