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

The authors examined the activity of N-acetyltransferase and that of microsomal P-450 isoenzymes in health and hepatic disease state by determining the acetylation phenotype and the total (CL(AP)) and metabolic clearances of antipyrine to form norantipyrine or N-demethylantipyrine (MCL(nora)), 3-hydroxymethylantipyrine (MCL(hma)), and 4-hydroxyantipyrine (MCL(ha)) in 21 healthy subjects and in 33 patients with chronic liver diseases (CLD) and investigated the relationship between the activities of these two enzyme systems. The acetylation phenotype was determined according to the urinary caffeine metabolites test. The mean and (SEM) of CLAP, MCL(hma), MCL(ha), and MCL(nora) in healthy subjects 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 of fast acetylation among the healthy subjects and patients with CLD was 38% and 39%, respectively. Although all metabolic clearances appear to be reduced in healthy slow acetylators, the reduction was only significant in MCL(nora), indicating a direct association between the activity of N-acetyltransferase and that of P-450 IIIA3 responsible for the N-demethylation of antipyrine. Conversely, slow acetylators with CLD exhibited significantly higher CLAP and near-significantly larger metabolic clearances including MCL(nora), which suggests that P-450 activity in fast acetylators is more sensitive to chronic liver diseases than in slow acetylators.