Previous in vivo and in vitro studies have indicated that the K(m) for phenytoin hydroxylation is about 30 μM. Yet, the drug shows dose-dependent kinetics suggesting a K(m) of about 5 μM. The present studies indicate the discrepancy is not due to active transport of the drug in the hepatocyte or a decrease in the K(m) due to the low pO2 of the portal vein leading to uncompetitive inhibition. Studies in both hepatocytes and microsomes indicate the presence of a high affinity hydroxylase with a K(m) of 2 to 5 μM. These data suggest that this enzyme is the one primarily involved in the metabolism of phenytoin.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1982|