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Maturation of AFMU excretion in infants
1Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent-de-Paul, Paris, France.
Insights
Infant N-acetyltransferase activity matures by 1 year of age. This study on caffeine metabolism in infants suggests acetylator status determination is unreliable before age one.
Area of Science:
- Pharmacology
- Pediatrics
- Biochemistry
Background:
- Caffeine is used to treat apnea in infants.
- N-acetyltransferase (NAT) enzyme activity, responsible for metabolizing drugs like caffeine, matures during infancy.
- Determining an infant's acetylator status is crucial for personalized medicine.
Purpose of the Study:
- To investigate the maturation of N-acetyltransferase-dependent metabolism of caffeine in infants.
- To determine the age at which reliable acetylator status can be assessed in pediatric populations.
Main Methods:
- Urine samples were collected from 14 infants (4 premature, 10 full-term) aged 1-19 months receiving caffeine citrate for apnea.
- High-performance liquid chromatography (HPLC) was used to measure caffeine, AFMU (a metabolite), and other compounds.
- The ratio of AFMU to 1X (another metabolite) was analyzed in relation to infant age.
Main Results:
- The AFMU/1X ratio, indicating NAT activity, showed no significant variation with age across the studied infant population.
- However, serial measurements in one infant revealed a dramatic increase in the AFMU/1X ratio between 6 and 12 months of age.
- This suggests a significant maturation of NAT activity occurs within this period.
Conclusions:
- N-acetyltransferase activity maturation is not complete before one year of age.
- Acetylator status cannot be reliably determined in infants younger than one year.
- Infants under one year with an AFMU/1X ratio below 0.4 may be either slow acetylators or immature fast acetylators.
Abstract:
The maturation of the N-acetyltransferase-dependent AFMU production from caffeine was studied during infancy. The group of children (N = 14) consisted of 4 premature newborn infants and ten 1-19 month-old infants who received caffeine citrate solution for the treatment and prevention of apnea. Caffeine, AFMU, 1X and 9 other metabolites were measured in urine using HPLC. The AFMU/1X ratio did not vary significantly in this population with increasing age. In one of the infants serially studied, the AFMU/1X ratio increased dramatically between 6 and 12 months of age. This observation suggests that the maturation of N-acetyltransferase activity is not completed before 1 year of age implying that acetylator status cannot reliably be determined before that age. Patients studied before 1 year of age whose AFMU/1X ratio was below 0.4 may be either true slow acetylators or still immature fast acetylators.