Dose-dependent metabolism of methotrexate in man and rhesus monkeys
- PMID: 406997
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Dose-dependent metabolism of methotrexate in man and rhesus monkeys
Cancer Treat Rep.
1977 Jul.
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).
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