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.