Maturation of caffeine metabolic pathways in infancy

The maturation of the different pathways of caffeine metabolism was studied during infancy. The group of children (n = 14) consisted of four premature newborn infants and 10 older infants who received caffeine citrate solution. Caffeine and 11 of its metabolites were measured by HPLC. Total demethylation and N 3‐ and N 7‐demethylation increase exponentially with postnatal age; the plateau is reached by 120 days and accounts for 58.6%, 90.5%, and 79.3%, respectively. N 1‐demethylation shows no variation with postnatal age. It is suggested that N 3‐demethylation is more important in young infants than in adults and that maturation of N 1‐demethylation occurs later than 19 months of age. 8‐Hydroxylation is mature as early as 1 month of age and may be higher in infants than in adults. Acetylation is not mature before at least 1 year of age. Differences in maturation rate of acetylation may be related in part to genetic acetylator status. Clinical Pharmacology and Therapeutics (1988) 44 , 145–151; doi: 10.1038/clpt.1988.129