title: Changes in theophylline metabolism during postnatal development in rat liver slices.
abstract: The metabolism of theophylline was studied in liver slices of young and adult rats. Theophylline and six metabolite fractions were recognized in adult liver by thin-layer radiochromatography and high performance liquid chromatography: 1-methyluric acid; 1-methylxanthine; 1,3-dimethyluric acid and/or 3-methylxanthine; caffeine; a uracil derivative and two unknown polar compounds. Preincubation with caffeine or theobromine inhibited theophylline metabolism. Allopurinol decreased the formation of three metabolite fractions but markedly increased the production of 1-methylxanthine. SKF 525-A inhibited the overall metabolism of theophylline. The specific activity of the enzyme system was 3.2 +/- 0.4 nmoles X (g liver)-1 X hr-1 in the 4- to 5-day-old rat and increased to a peak of 25.7 +/- 1.7 in the 28-day-old; values for Km and Vmax in the 7- and 28-day-olds were 132.1 and 67.5 microM, and 23.9 and 52.1 nmoles X (g liver)-1 X hr-1 respectively. Theophylline and the same six metabolites were identified in young and adult rats, but the development pattern was not uniform. Peak age-related activity and involvement of mixed-function oxidase system are features which are common to theophylline and caffeine metabolism. Xanthine oxidase played a role in theophylline metabolism. Formation of caffeine from theophylline was not dependent on a lack of activity of other pathways.
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008099:Liver / Q000378:metabolism*; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D013805:Theobromine / Q000494:pharmacology; D013806:Theophylline / Q000378:metabolism*
chemical_list: D002110:Caffeine; D000493:Allopurinol; D011335:Proadifen; D013806:Theophylline; D013805:Theobromine