Dose-dependent kinetics of theophylline disposition in asthmatic children (original) (raw)

TheJournalofPEDIATRICS Dose-dependent kinetics of theophylline disposition in asthmatic children Prior assumptions of first-order elimination for theophylline were tested by administering theophylline by intravenous infitsion at two dosage levels to 20 children with chronic asthma. The resulting steadystate serum concentrations increased to a greater degree than would have been predicted if increases in serum concentration were proportional to changes in dose, and the subsequent calculation of clearance revealed values ofl.37 • 0.09 ml/kg/minute (mean • SE of the mean) at the lower infusion rate and of 1.21 ~ 0.06 ml/kg/minute at the higher infusion rate (lo < 0.02). Even greater differences in clearance were present among ten of these children whose higher infitsion rates were at least two times greater than the lower rate. A n additional child was observed who experienced a seizure following a medication error that resulted in a 50% increase in daily dosage and a greater than threefold increase of serum concentration. The nonlinear nature of the relationship between dose and serum concentration suggests that theophylline dosage adjustment should be performed cautiously using small increments.