PT  - JOURNAL ARTICLE
AU  - M Jurima
AU  - T Inaba
AU  - W Kalow
TI  - Mephenytoin metabolism in vitro by human liver.
DP  - 1985 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 151--155
VI  - 13
IP  - 2
4099  - http://dmd.aspetjournals.org/content/13/2/151.short
4100  - http://dmd.aspetjournals.org/content/13/2/151.full
SO  - Drug Metab Dispos1985 Mar 01; 13
AB  - Human liver was used in investigations of mephenytoin p-hydroxylase, the enzyme presumably responsible for the genetic polymorphism in mephenytoin metabolism. A gas chromatographic assay method was developed to measure p-hydroxylation and N-demethylation which is the other major metabolic pathway. Both reactions were localized in the microsomal fraction and required NADPH. Inhibition of p-hydroxylation by CO, SKF 525-A, and metyrapone was demonstrated. It was concluded that a form of cytochrome P-450 catalyzes the reaction. The velocity of N-demethylation in human liver did not show saturation even at 500 microM substrate concentration. The p-hydroxylation, however, followed Michaelis-Menten kinetics. The Km, determined in five different livers, ranged from 59 to 143 microM. The linearity in Eadie-Hofstee plots was consistent with the involvement of a single catalytic site.