S A Jacobs, R G Stoller, B A Chabner, D G Johns
J Clin Invest.
1976;
57(2):534–538
doi:10.1172/JCI108308
This article Copyright © 1976, The American Society for Clinical Investigation
Abstract
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H
uman subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug.
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