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

J Clin Invest. 1976 Feb;57(2):534-8. doi: 10.1172/JCI108308.


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.

MeSH terms

  • 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


  • 7-hydroxymethotrexate
  • Methotrexate