Metabolism of caffeine to 6-amino-5-[N-methylformyl-amino]-1, 3-dimethyluracil in the isolated, perfused liver from control or phenobarbital-, β-naphthoflavone- and 3-methylcholanthrene-pretreated rats

A. Guaitani, R. Abbruzzi, A. Bastone, M. Bianchi, M. Bonati, P. Catalani, R. Latini, C. Pantarotto, K. Szczawinska

Research output: Contribution to journalArticlepeer-review

Abstract

Caffeine metabolism to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was studied in the isolated, perfused rat liver. The [2-14C]-labelled drug and metabolites were separated by thin-layer chromatography or high-pressure liquid chromatography. The chemical structure of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was confirmed by mass spectrometry and it was quantitatively determined by liquid scintillation counting. 6-Amino-5-[N-methylformylamino]-1,3-dimethyluracil is one of the major metabolites of caffeine found in the perfusion medium. The kinetics of caffeine elimination and of the uracil metabolite formation were studied up to 2 h perfusion time using livers from control rats and rats pretreated with phenobarbital, β-naphthoflavone or 3-methylcholanthrene. Phenobarbital pretreatment did not modify the rate of caffeine elimination or the extent of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil formation. In contrast, there was a highly significant inducing effect on both drug elimination and formation of the uracil metabolite in perfusions of livers from β-naphthoflavone- and 3-methylcholanthrene-pretreated animals.

Original languageEnglish
Pages (from-to)55-66
Number of pages12
JournalToxicology Letters
Volume38
Issue number1-2
DOIs
Publication statusPublished - 1987

Keywords

  • caffeine metabolism
  • induction
  • isolated perfused liver
  • Rat

ASJC Scopus subject areas

  • Toxicology

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