title: Dose-dependent metabolism of methotrexate in man and rhesus monkeys.
abstract: Humans and rhesus monkeys receiving high-dose methotrexate (MTX) (greater than 50 mg/kg) excrete significant quantities of the metabolite, 7-hydroxy-MTX. This metabolite, though 200-fold less potent than MTX as an inhibitor of mammalian dihydrofolate reductase, is of very limited aqueous solubility, and thus may contribute to the renal toxicity of the high-dose regimen. The metabolite was not observed in previous pharmacologic studies in which conventional doses of MTX were administered (less than 10 mg/kg).
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D000882:Haplorhini; D006801:Humans; D006900:Hydroxylation; D007263:Infusions, Parenteral; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta; D008727:Methotrexate / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged
chemical_list: D008727:Methotrexate