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 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.
Carrier
O
O
Department of Clinical Pharmacology, Hôpital Saint-Vincent de Paul, Paris, France.
Pons
G
G
Rey
E
E
Richard
M O
MO
Moran
C
C
Badoual
J
J
Olive
G
G
D000107:Acetylation; D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D001049:Apnea / Q000188:drug therapy / Q000517:prevention & control; D002110:Caffeine / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002951:Citrates / Q000008:administration & dosage / Q000378:metabolism; D004338:Drug Combinations / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008297:Male; D010855:Pierre Robin Syndrome / Q000188:drug therapy; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine; D014970:Xanthines / Q000652:urine
D002951:Citrates; D004338:Drug Combinations; D014970:Xanthines; C008514:methylxanthine; D002110:Caffeine; D014498:Uracil; C036692:5-acetylamino-6-formylamino-3-methyluracil; C026189:caffeine citrate