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

Toxicology Letters
A GuaitaniK Szczawinska

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, beta-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 beta-naphthoflavone- and 3-methylcholanthrene-pretreated animals.

References

Oct 1, 1977·Life Sciences·A AldridgeA H Neims
Aug 1, 1973·Teratology·J J Mulvihill
Jul 1, 1972·Toxicology and Applied Pharmacology·T Fujii, H Nishimura
Jul 1, 1968·Cancer·H J Norris, H B Taylor
Aug 1, 1980·The Journal of Pharmacy and Pharmacology·R LatiniA Bizzi
Jan 1, 1981·Toxicology·L G CostaS D Murphy
May 1, 1960·Proceedings of the Society for Experimental Biology and Medicine·H NISHIMURA, K NAKAI

Citations

Jan 11, 1991·Pflügers Archiv : European journal of physiology·T HisadaJ V Walsh

Related Concepts

6-amino-5-(formyl-N-methylamino)-1,3-dimethyluracil
Metazoa
Benzoflavones
Metabolic Biotransformation
Quick-Pep
High Pressure Liquid Chromatography Procedure
Drug Interactions
Liver
Methylcholanthrene
Luminal

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