Pharmacokinetic analysis of the disposition of intravenous theophylline in young children.

The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The man plasma theophylline clearance was 0.100 +/- 0.036 l/kg/hr, kel 0.49 +/- 0.30 hr-1, betat1/2 3.38 +/- 1.11 hr, alphat1/2 0.13 +/- 0.09 hr, and V1 0.25 +/- 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost identical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetic constants predict that a maintenance dose rate for aminophylline of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/1. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement of steady state) have not yet been conducted.