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Abstract
1. Caffeine was used as a molecular probe for hepatic monooxygenase activity in three in vitro models from human livers: slices, microsomes and hepatocyte cultures.
2. A h.p.l.c. method for determination of all possible metabolites of caffeine (16 compounds) is described.
3. Caffeine biotransformation by these three in vitro systems was low. However, metabolite formation was shown to proceed at a rate close to that calculated from in vivo caffeine elimination half-life.
4. Metabolic profiles were the same whatever the in vitro system used. The ratio of primary demthylated metabolites was similar to that measured by in vivo studies, i.e. the selectivity for caffeine N-3 demethylation to paraxanthine was retained.
5. Significant correlation (p<0.001) between 7-ethoxyresorufin O-deethylation and caffeine demethylations was demonstrated for the 12 human livers studied.