CAFFEINE METABOLISM IN A HEALTHY SPANISH POPULATION - N-ACETYLATOR PHENOTYPE AND OXIDATION PATHWAYS

We studied the oxidative and N-acetylator caffeine metabolic profile i n 107 healthy Spanish volunteers. Smokers had significantly higher N-1 - and N-3-demethylations activities than nonsmokers (p = 0.03 and p = 0.02, respectively), and the three caffeine demethylations indexes wer e strongly correlated with each other (r > 0.7; p < 0.001). Our in viv o studies suggest that CYP1A2 is involved, at least in part, in the pr imary N-demethylations of caffeine. A non-normal and possibly bimodal distribution was detected in the xanthine oxidase activity (p = 0.04), with about 4% of subjects deficient of this metabolic activity. The p opulation exhibited a trimodal distribution of acetylator phenotype de termined by use of the cetylamino-6-amino-3-methyluracil/1-methylxanth ine ratio (normality test; p = 0.004). Seventy subjects (65.4%) were p henotyped as slow acetylators. The mutated gene frequency was 0.81, wh ich is similar to other white populations.