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Caffeine acetylator phenotyping during maturation in infants
A Pariente-Khayat1, G Pons, E Rey
1Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, Paris, France.
Insights
Caffeine metabolism in children matures with age, with slow acetylator phenotypes common in infants. This study tracked caffeine acetylator phenotypes in children, finding a significant increase in fast acetylators as they age.
Area of Science:
- Pharmacology
- Pediatrics
- Biochemistry
Background:
- Caffeine acetylator phenotype influences drug metabolism.
- Understanding pediatric drug metabolism is crucial for safe and effective treatment.
- Maturation of metabolic pathways in children can alter drug responses.
Purpose of the Study:
- To investigate the development of caffeine acetylator phenotype during childhood.
- To determine the age-related changes in caffeine metabolism in pediatric populations.
- To compare caffeine acetylation in healthy children and those with Pierre Robin syndrome.
Main Methods:
- Phenotyping caffeine acetylator status using urinary metabolite ratios (AFMU/1-methylxanthine and other metabolite ratios) via High-Performance Liquid Chromatography (HPLC).
- Studied 54 children (8-447 days) with minor illnesses and 5 children with Pierre Robin syndrome.
- Serial phenotyping was conducted in children with Pierre Robin syndrome receiving chronic caffeine therapy.
Main Results:
- All infants under 83 days were slow acetylators; older children exhibited both slow and fast acetylator phenotypes.
- Caffeine acetylation ratios significantly increased with age, indicating a maturing metabolic capacity.
- The proportion of fast acetylators increased with age, though a plateau was not reached by 15 months.
Conclusions:
- Caffeine acetylator phenotype undergoes significant maturation during infancy and early childhood.
- Age is a critical factor in determining caffeine metabolic capacity in children.
- Individual variations in maturation exist, with some children transitioning from slow to fast acetylators over time.
Abstract:
Caffeine acetylator phenotype was studied during maturation in 54 8- to 447-d-old children hospitalized for minor disease (group A) and in five 3- to 630-d-old children with Pierre Robin syndrome (group B). In group A, the children received 2.5 mg/kg caffeine orally once between birth and 15 mo. Group B patients were chronically treated with caffeine (2.3 to 15.8 mg/kg/d) for prevention of apneas, and the acetylator phenotype was serially determined. Phenotyping was performed on a spot urine sample collected 2-6 h after drug administration. Caffeine metabolites [5-acetylamino-6-formylamino-3-methyl uracil (AFMU), 1-methylxanthine, 1-methyluric acid, 1,7-methyluric acid, and 1,7-methylxanthine] were measured using HPLC. Acetylator phenotype was determined on the basis of AFMU/1-methylxanthine (ratio 1) and AFMU/AFMU + 1,7-methyluric acid + 1-methylxanthine + 1,7- methylxanthine + 1,7-methyluric acid (ratio 2) molar ratios. In group A, all children were slow acetylators before 83 d of age (ratio 1 less than 0.4; ratio 2 less than 0.08), whereas older children included slow and fast acetylators. The acetylation molar ratios differed significantly between age groups and increased with age. The cumulative percentage of fast acetylators increased with age but the plateau was not yet reached at 15 mo. In three children, the phenotyping was repeated after 15 mo: the second determination was consistent with the first one. In group B, all children appeared as slow acetylators on the first phenotyping. Four of them appeared subsequently as fast acetylators; one remained a slow acetylator until 11 mo.(ABSTRACT TRUNCATED AT 250 WORDS)