Evaluation of theophylline clearance in children with bronchial asthma

Abstract

The total body clearance of theophylline was examined in 95 children aged 6 months to 15 years with chronic bronchial asthma. Each patient received sustained-release theophylline preparations and was evaluated at steady state. Blood samples were obtained 1-8 hours after a morning dose, and individual total body clearance was determined with a Bayesian forecasting computer model. Changes in theophylline clearance were evaluated within age groups, with the age determined at the time of blood sampling. Total body clearance tended to increase with age up to 10 years. In children over 10 years old, total body clearance significantly decreased with age. The interpatient variability of theophylline clearance was most noticeable at 2-4 years of age. Changes in volume of distribution were similar to those in clearance. In conclusion, there are pronounced age-dependent differences in theophylline clearance that require individual adjustment of dosage regimens on the basis of serum concentrations and clinical response in children. Individualization of the oral dose based on frequent serum measurements is necessary to maintain theophylline levels in the therapeutic range.