ACETYLATOR PHENOTYPING - THE URINARY CAFFEINE METABOLITE RATIO IN SLOW ACETYLATORS CORRELATES WITH A MARKER OF SYSTEMIC NAT1 ACTIVITY

Eighteen healthy Caucasians were evaluated for the systemic acetylatio n of a caffeine metabolite using the urinary caffeine metabolite ratio 5-acetylamino-6-formylamino-3-methylurac (AFMU) to 1-methylxanthine ( 1X) and for N-acetyltransferase activity in peripheral blood mononucle ar leukocytes (MNL) using p-aminobenzoic acid (PABA). These are marker s for systemic NAT2 and NAT1 N-acetyltransferase activities, respectiv ely. Fourteen slow acetylators and four fast acetylators (the NAT2 pol ymorphism) were identified by the caffeine metabolite ratio. In slow a cetylators who have decreased levels of hepatic NAT2, the AFMU/1X rati o was significantly correlated with PABA acetylation in MNL (r =0.8; p = 0.0002). These results suggest that significant variation in the ac etylation of arylamine substrates susceptible to the classical acetyla tor polymorphism is attributable to variation in NAT1 activity in the slow acetylator phenotype.