Theophylline metabolism during the first month of life and development

The metabolic pathway of theophylline (T) was studied in 12 newborns, one young infant, six children, and three adult volunteers. T was injected IV, and blood and urine samples were assayed for T, caffeine (C), and their metabolites by a highpressure liquid chromatography technique. We confirmed the methylation of T to C in newborn infants but not in older subjects. Demethylation of T to 3-methylxanthine was found in the young infant, in children, and in adults, but not in newborns. The major products excreted by neonates were T, 1-methyluric acid, and 1,3-dimethyluric acid. Children excreted a larger fraction of methyluric acids than adults. Renal and body clearance of T and C are reported and discussed in relation to the age. Speculation: On the grounds of blood and urine samples from subjects treated with theopylline, our results could indicate that caffeine oxidation predominates over A’-demethylation, involving lower activity of the cytochrome P-450 monooxygenase system during the first month of life than in older infants or adults compared to data reported in literature for other drugs. Our results suggest different forms of enzymes are involved in these reactions.