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  • Title: Caffeine demethylase activity in human and Dark Agouti rat liver microsomes. Comparison with aminopyrine N-demethylase activity.
    Author: Agúndez JA, Luengo A, Benítez J.
    Journal: Drug Metab Dispos; 1992; 20(3):343-9. PubMed ID: 1521502.
    Abstract:
    Human and Dark Agouti rat liver microsomes were analyzed for caffeine metabolism focusing on demethylase activity by using a simplified isocratic HPLC method. Results showed that, despite interspecies quantitative and qualitative differences on caffeine metabolism, mainly demethylated caffeine metabolites were detected in both species. Humans showed interindividual quantitative differences in caffeine demethylase activity in contrast to rats and, in both cases, the proportion of metabolites remained constant. In addition, aminopyrine N-demethylase activity was assayed, showing a direct correlation with caffeine demethylase activity in humans (r = 0.71) that is reported here for the first time, but not in rats (r = 0.21). These results indicate that, in human liver microsomes, caffeine and aminopyrine could be demethylated by the same or by closely related enzymes; whereas in Dark Agouti rats, there is no apparent relation between caffeine and aminopyrine demethylation pathways.
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