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 language | English |
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Pages (from-to) | 55-66 |
Number of pages | 12 |
Journal | Toxicology Letters |
Volume | 38 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - 1987 |
Keywords
- caffeine metabolism
- induction
- isolated perfused liver
- Rat
ASJC Scopus subject areas
- Toxicology