The effect of methotrexate on folate metabolism in the rat

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Abstract
The metabolism of 2-[14C]-folic acid, 2-[14C]-5-methyltetrahydrofolate 5-[14C]-methyltetrahydrofolate, and a mixture of 2-[14C]-folic acid and 3',5',7,9-[3H]-folic acid has been studied in rats that were dosed with methotrexate (MTX) 24 h before receiving the radioactive folate. Methotrexate increases urinary excretion of radioactivity in rats given 2-[14C]-folic acid, but there was no significant increase in urinary radioactivity in animals given 5-methyltetrahydrofolate. Animals dosed with MTX had less of the dose in the liver, and excreted more of the dose via the faeces. These results are consistent with the known biochemical effects of methotrexate. Experiments with a mixture of 2-[14C]-folic acid and 3',5',7,9-[3H]-folic acid indicate that there is an increase in scission of the folate molecule following a dose of MTX.