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The metabolism of phenytoin by isolated hepatocytes and hepatic microsomes from male rats

Tsuru, M.; Erickson, R.R.; Holtzman, J.L.

Journal of Pharmacology and Experimental Therapeutics 222(3): 658-661

1982

ISSN/ISBN: 0022-3565
PMID: 7108769
Document Number: 187775
Previous in vivo and in vitro studies have indicated that the Km for phenytoin hydroxylation is about 30 microM. Yet, the drug shows dose-dependent kinetics suggesting a Km of about 5 microM. The present studies indicate the discrepancy is not due to active transport of the drug in the hepatocyte or a decrease in the Km 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 Km of 2 to 5 microM. These data suggest that this enzyme is the one primarily involved in the metabolism of phenytoin.

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