TY - JOUR T1 - N-acetylation pharmacogenetics. Michaelis-Menten constants for arylamine drugs as predictors of their N-acetylation rates in vivo. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 382 LP - 385 VL - 14 IS - 4 AU - H H Andres AU - W W Weber Y1 - 1986/07/01 UR - http://dmd.aspetjournals.org/content/14/4/382.abstract N2 - Michaelis-Menten constants for two in vivo monomorphically N-acetylated substrates, p-aminobenzoic acid and p-aminosalicylic acid, and two in vivo polymorphically N-acetylated substrates, sulfamethazine and procainamide, were determined with an improved assay procedure using liver N-acetyltransferase from rapid and slow acetylator rabbit. The slow rabbit liver isozyme proves to be a Vmax and a Km variant for p-aminobenzoic acid and p-aminosalicylic acid. Mean differences in the apparent Vmax for rapid acetylators were 39-fold greater for p-aminobenzoic acid and 16-fold greater for p-aminosalicylic acid. The apparent Km values for the slow acetylator enzyme were lower than 5 microM, whereas the apparent Km values for the rapid acetylator phenotype were at least 15 times higher, with a value of 105 +/- 21 microM for p-aminobenzoic acid and 74 +/- 16 microM for p-aminosalicylic acid. In contrast, for the polymorphic substrates, sulfamethazine and procainamide, rapid rabbit liver N-acetyltransferase was only a Vmax variant with a mean specific activity that was 13-fold higher than that for slow acetylator. ER -