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

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 t...

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Bibliographic Details
Published inThe Journal of clinical investigation Vol. 57; no. 2; pp. 534 - 538
Main Authors Jacobs, S A, Stoller, R G, Chabner, B A, Johns, D G
Format Journal Article
LanguageEnglish
Published United States 01.02.1976
Subjects
Adult
Animals
Bone Neoplasms - drug therapy
Carcinoma, Squamous Cell - drug therapy
Child
Female
Histocytochemistry
Humans
Kidney - metabolism
Lung Neoplasms - drug therapy
Macaca mulatta
Male
Methotrexate - administration & dosage
Methotrexate - analogs & derivatives
Methotrexate - metabolism
Methotrexate - therapeutic use
Methotrexate - urine
Middle Aged
Osteosarcoma - drug therapy
Time Factors
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ISSN0021-9738
DOI10.1172/JCI108308

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Summary: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.
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ISSN:0021-9738
DOI:10.1172/JCI108308