Caffeine metabolism in a healthy Spanish population: N-acetylator phenotype and oxidation pathways.
We studied the oxidative and N-acetylator caffeine metabolic profile in 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 were strongly correlated with each other (r > 0.7; p < 0.001). Our in vivo studies suggest that CYP1A2 is involved, at least in part, in the primary 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 population exhibited a trimodal distribution of acetylator phenotype determined by use of the 5-acetylamino-6-amino-3-methyluracil/1-methylxanthine ratio (normality test; p = 0.004). Seventy subjects (65.4%) were phenotyped as slow acetylators. The mutated gene frequency was 0.81, which is similar to other white populations.
Carrillo
J A
JA
Departamento de Farmacología y Psiquiatría, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.
Benítez
J
J
D000107:Acetylation; D000328:Adult; D002110:Caffeine / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D010641:Phenotype; D012016:Reference Values; D013030:Spain; D013997:Time Factors
D002110:Caffeine