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  • Title: Developmental changes in urinary elimination of theophylline and its metabolites in pediatric patients.
    Author: Tateishi T, Asoh M, Yamaguchi A, Yoda T, Okano YJ, Koitabashi Y, Kobayashi S.
    Journal: Pediatr Res; 1999 Jan; 45(1):66-70. PubMed ID: 9890610.
    Abstract:
    We investigated the developmental changes in the pattern of urinary metabolites of theophylline, a substrate for CYP1A2, to study when CYP1A2, which is absent in the perinatal period, fully develops during childhood. The urinary ratios of three metabolites (1-methyluric acid, 3-methylxanthine, and 1,3-dimethyluric acid) to theophylline in patients over 3 y of age show a much larger interindividual variation compared with those under 3 y of age, and the mean values of the ratios in patients over 3 y of age were greater than those in patients under 1 y of age. The urinary ratio of 1,3-dimethyluric acid (a metabolite generated by several cytochrome P450s) to 3-methylxanthine or 1-methyluric acid (metabolites generated by CYP1A2 exclusively) seemed to be relatively constant over 3 y of age; in patients under 3 y of age, these ratios were much higher than those in patients over 3 y of age. The urinary ratio of 1-methyluric acid to 3-methylxanthine or 3-methylxanthine to 1-methyluric acid seemed to be relatively invariable in all patients except those less than 1 y of age. These findings suggest that CYP1A2 activity may be programmed to mature by around 3 y of age and that CYP1A2 probably plays a major role in theophylline 8-hydroxylation at a therapeutic concentration after the full development of CYP1A2 activity.
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