RELATIONSHIP BETWEEN ANTIPYRINE METABOLISM AND ACETYLATION PHENOTYPE IN HEALTH AND CHRONIC LIVER-DISEASES

The authors examined the activity of N-acetyltransferase and that of m icrosomal P-450 isoenzymes in health and hepatic disease state by dete rmining the acetylation phenotype and the total (CL(AP)) and metabolic clearances of antipyrine to form norantipyrine or N-demethylantipyrin e (MCL(nora)), 3-hydroxymethylantipyrine (MCL(hma)), and 4-hydroxyanti pyrine (MCL(ha)) in 21 healthy subjects and in 33 patients with chroni c liver diseases (CLD) and investigated the relationship between the a ctivities of these two enzyme systems. The acetylation phenotype was d etermined according to the urinary caffeine metabolites test. The mean and (SEM) of CLAP, MCL(hma), MCL(ha), and MCL(nora) in healthy subjec ts were 2.42 (0.264), 0.193 (0.031), 0.322 (0.045), and 0.288 (0.04) L /h, and those observed in patients with CLD were 0.98 (0.1), 0.076 (0. 015), 0.131 (0.026), 0.103 (0.022) L/h, respectively. The prevalence o f fast acetylation among the healthy subjects and patients with CLD wa s 38% and 39%, respectively. Although all metabolic clearances appear to be reduced in healthy slow acetylators, the reduction was only sign ificant in MCL(nora), indicating a direct association between the acti vity of N-acetyltransferase and that of P-450 IIIA3 responsible for th e N-demethylation of antipyrine. Conversely, slow acetylators with CLD exhibited significantly higher CLAP and near-significantly larger met abolic clearances including MCL(nora), which suggests that P-450 activ ity in fast acetylators is more sensitive to chronic liver diseases th an in slow acetylators.