Determination of N-acetylation phenotyping in a Greek population using caffeine as a metabolic probe

Studies of isoniazid, the well known antituberculosis drug, have revealed t hat N-acetylation polymorphism, is of great clinical importance. In humans, N-acetylation is one of the most important pathways in the inactivation of isoniazid. Caffeine, which is also biotransformed by N-acetylation, has be en widely used as an in vivo probe for the assessment of N-acetyltransferas e polymorphism. The activity of N-acctyltransferase can be estimated from t he urinary metabolic ratio of two caffeine metabolites, namely, 5-acetylami no-6-formy-lamino-3-methyluracil (AFMU), and 1-methylxanthine (1X) after th e ingestion of caffeine. In the present study caffeine was used as a metabolic probe to determine N- acetyltransferase polymorpism in 83 healthy Creek volunteers by means of th e molar ratio of AFMU and 1X determined in urine following ingestion of 200 mg caffeine. Frequency distribution analysis of the metabolic ratios AFMU/ 1X revealed two distinct groups with 66.3% (n = 55) slow acetylators and 33 .7 % (n = 28) rapid acetylators. No statistically significant difference wa s detected between slow and fast acetylators in terms of gender, smoking ha bits and caffeine-intake habits. These results are in agreement with previo us studies on N-acetyltransferase activity in Caucasians using caffeine as a metabolic probe. They also agree with reports on N-acetyltransferase acti vity in Greek tuberculosis patients using isoniazid as a metabolic probe. T hus, the use of caffeine as a metabolic probe is a reliable method for the assessment of N-acetyltransferase activity in the Greek population.