RT Journal Article
SR Electronic
T1 Mephenytoin metabolism in vitro by human liver.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 151
OP 155
VO 13
IS 2
A1 M Jurima
A1 T Inaba
A1 W Kalow
YR 1985
UL http://dmd.aspetjournals.org/content/13/2/151.abstract
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.