EFFECT OF AGE ON THEOPHYLLINE CLEARANCE AND DOSAGE REQUIREMENTS DURING CHILDHOOD

Previous recommendations for weight adjusted theophylline dosage have not considered age as a contributing variable. The current data was collected in two parts. First, 23 children with chronic asthma, ages 4-15, received .8 mg/kg/hr intravenous infusions of theophylline until steady-state serum concentrations were documented. Clearance was then calculated (clearance = infusion rate % steady-state serum concentration). Subsequently, 156 children with chronic asthma, ages 2½ months to 16 years, received chronic oral theophylline in 4 doses/day titrated to achieve peak serum concentrations in the therapeutic range of 10 to 20 μg/ml (mean was 15 μg/ml). Clearances among the 23 children receiving the intravenous infusion averaged 1.35 ± .46 ml/kg/min (mean ± standard deviation), but correlated inversely with age (rS = −.46, p < .025). The 7 children over age 12 averaged .88 ± .25 ml/kg/min while the younger children averaged 1.56 ± .37 ml/kg/min. Mean oral dosage requirements also varied with age. Seventy-seven children under age 9 required 24.1 ± 5.5 mg/kg/day of theophylline to maintain therapeutic levels, and no significant correlation with age was observed in this group. Among the 79 children from 9-16 years of age. however, doses averaged 19.4 ± 4.9 mg/kg/day and correlated significantly with age (r = −.32, p < .01). Thus, weight adjusted dosage guidelines for theophylline must be age specific.