Maturation of caffeine metabolic pathways in infancy

Abstract

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 N3- and N7-demethylation increase exponentially with postnatal age; the plateau is reached by 120 days and accounts for 58.6%, 90.5%, and 79.3%, respectively. N1-demethylation shows no variation with postnatal age. It is suggested that N3-demethylation is more important in young infants than in adults and that maturation of N1-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.

CO(2) Breath Tests Using 14C-Caffeine, 14C-Methacetin and 14C-Phenacetin for Assessing Postnatal Development of Monooxygenase Activities in Rats and Marmosets

“…Al though it is difficult to compare metabolic capacities of newborn of various species be cause of differences in the degree of matura tion, it is interesting to note that 14CC>2 for mation (breath test) from caffeine is gener ally very low at birth. This agrees with data obtained in human newborn [20][21][22], who also metabolize caffeine very poorly. In con trast, 14C02 formation (breath test) from la belled methacetin was found to be readily measurable in rats and especially in marmo…”

“…The inability of human newborn to me tabolize caffeine have been shown by in vivo studies [20,21], Furthermore, data on caf feine breath tests have been published for only a few newborn [22], However, the post natal development of these monooxygenase activities in the rat and nonhuman primates, as measured with labelled caffeine, phenace tin or methacetin in a breath test, has not yet been systematically investigated.…”

Genetic polymorphism of CYP2D6 in a Keralite (South India) population

“…This enzyme is not mature until 4 months of age [11] and in newborns even a low exposure of CYP1A2 substrate might therefore constitute a possible risk for adverse drug reactions. Due to ethical reasons we did not obtain blood samples in this infant, but no adverse drug reaction or unusual behaviour were observed, as was reported for the two previously exposed infants [7,8].…”

“…Urine was collected overnight for 8 h. A 20 ml aliquot was stored at ±208 C until analysis for dextromethorphan (DM) and dextrorphan (DT) by h.p.l.c [11]. The inter and intraday coef®cient of variation for assay of DM and DT (50±8000 ng ml ±1 ) were less than 10% and 5%, respectively.…”

Sequential Updating of a New Dynamic Pharmacokinetic Model for Caffeine in Premature Neonates

“…Its main parameters are the volume of distribution and the caffeine clearance. Moreover, as volume of distribution (depending on the amount of total body water) and metabolism change significantly during the few weeks of the treatment [20][21][22] , we propose a dynamic model with time-dependent parameters.…”