Changes in theophylline metabolism during postnatal development in rat liver slices

Rafael Gorodischer, Arie Yaari, Michal Margalith, Ditza Warszawski, Zvi Ben-Zvi

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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. Pre-incubation 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 · (g liver)-1· 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 μM, and 23.9 and 52.1 nmoles · (g liver)-1 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.

Original languageEnglish
Pages (from-to)3077-3081
Number of pages5
JournalBiochemical Pharmacology
Issue number18
StatePublished - 15 Sep 1986

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


Dive into the research topics of 'Changes in theophylline metabolism during postnatal development in rat liver slices'. Together they form a unique fingerprint.

Cite this