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Pediatr Res. 2006 Dec;60(6):717-23. Epub 2006 Oct 25.

Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants.

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1
Department of Pediatrics, University of Missouri-Kansas City, School of Medicine and the Division of Pediatric Pharmacology and Medical Toxicology, Children's Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA. mjblake@cmh.edu

Abstract

Orally administered caffeine and dextromethorphan (DM) were used as pharmacologic probes to determine the effect of infant diet on acquisition of cytochrome P-450 (CYP) enzyme activity during the first 6 mo of life. The caffeine elimination rate constant (ke) was determined from serum, and concentrations of caffeine, DM, and their respective metabolites were measured in urine by high-performance liquid chromatography (HPLC). Caffeine ke was low at 2 wk and displayed a significant positive linear correlation with age (p < 0.001); increasing faster in formula-fed than in breast-fed infants (p < 0.001). This occurred concomitantly with a significant increase in urinary 1,7-dimethylxanthine (17X) and 1-methylxanthine (1X) (p < 0.001), suggesting faster acquisition of CYP1A2 activity in formula-fed infants. The urinary molar ratio of (17X + 1X)/caffeine and age strongly predicted caffeine ke (r2 = 0.65; p < 0.001) irrespective of feeding type. CYP3A4 activity, assessed as the molar ratio of 3-hydroxymorphinan/dextrorphan showed a similar marked increase with postnatal age (p < 0.001) that was also greater in formula-fed than in breast-fed infants. Formula feeding appears to accelerate maturation of caffeine and DM metabolism by increasing the activity of CYP1A2 and CYP3A4, respectively. Dietary modification of CYP activity may modulate drug biotransformation and thus alter systemic exposure to xenobiotics from a very early age.

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