Lack of low Km diazepam N-demethylase in livers of poor metabolizers for S-mephenytoin 4'-hydroxylation.

摘要: Metabolism of diazepam was studied in vitro to identify the forms cytochrome P450 (CYP) responsible for N-demethylation (nordazepam formation) and 3-hydroxylation (temazepam formation), using liver microsomes obtained from extensive (EM) poor metabolizers (PM) S-mephenytoin 4'-hydroxylation. Involvement at least two suggested by a biphasic pattern Lineweaver-Burk Eadie-Hofstee plots EM, whereas monophasic observed PM microsomes. The kinetic parameters EM group were: Km 1, 19.4 +/- 0.4 microM; Vmax 0.27 0.04 nmol min-1 per mg protein; 2, 346 34 Vmax2, 1.82 0.63 protein (n = 3, mean SD). showed values (Km, 319 30 Vmax, 1.49 0.62 protein) 3) similar those Km2 Vmax2 group. An antibody raised against CYP2C9 (anti-human CYP2C) strongly inhibited low substrate concentration (20 microM). However, anti-human CYP2C no clear inhibition high (200 Diazepam not clearly either or concentrations. These data suggest that different mediated microsomes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)