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J Clin Invest. 1976 Feb;57(2):534-8.

7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate.

Abstract

Human 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.

PMID:
1062383
PMCID:
PMC436681
DOI:
10.1172/JCI108308
[Indexed for MEDLINE]
Free PMC Article
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