Metabolism of methotrexate in man after high and conventional doses.

Methotrexate has been found to be extensively metabolized to 7-hydroxymethotrexate in patients receiving conventional doses (less than 10 mg/kg) and high doses (greater than 10 mg/kg). Twelve hours after administration, plasma levels of this metabolite in several patients treated with low doses exceeded those of methotrexate. No 7-hydroxymethotrexate was found in CSF after CNS administration of methotrexate; however, small amounts of the metabolite was found in the CSF after intravenous high dose infusion. We conclude that methotrexate is significantly metabolized in man at all doses used clinically.