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Methotrexate is an antineoplastic agent which acts as an antimetabolite of folic acid. It also has immunosuppressant properties. Within the cell, folic acid is reduced to dihydrofolic and then tetrahydrofolic acid. Methotrexate competitively inhibits the enzyme dihydrofolate reductase and prevents the formation of tetrahydrofolate which is necessary for purine and pyrimidine synthesis and consequently the formation of DNA and RNA.
When given in low doses, Methotrexate is rapidly absorbed from the gastro-intestinal tract, but higher doses are less well absorbed. Methotrexate is distributed to tissues and extracellular fluid. It penetrates ascitic fluid and effusions which may act as a depot and thus enhance toxicity. Methotrexate does not appear to undergo significant metabolism at low doses.
