Effect of age on patterns of theophylline metabolism

The pattern of excretion of urinary theophylline and theophylline metabolites were studied in three groups of patients (premature neonates, children, and adults). When adjusted to a standard dose of 10 mg/kg/day to allow valid comparison between groups, differeces in mean corrected trough plasma theophylline concentrations (corrected Cp) were found that were of similar magnitude to differences reported in theophylline clearance in these groups. Despite the lower corrected Cp in children, urinary theophylline metabolite patterns were similar in adults and children, indicating that the increased clearance in children is not associated with induction of a specific metabolic pathway. In premature neonates, only unchanged theophylline and caffeine were found in urine, indicating the absence of oxidative pathways for theophylline metabolism. In both adults and children, there was high positive correlation between urinary excretion of 3-methylxanthine (3MX) and 1-methyluric acid (1MU). Both 3MX and 1MU correlated negatively with urinary excretion of 1.3.-dimethyluric acid (DMU). It is suggested that N-demethylation of theophylline to 3MX and 1MU is catalyzed by a different form of cytochrome P-450 than that involved in the 8-hydroxylation to DMU.