Abstract
METHOTREXATE, a widely used and effective antineoplastic agent, is eliminated primarily by urinary excretion in man1. In species such as the rabbit, which possess hepatic enzymes capable of metabolizing methotrexate to inactive products, the drug is rapidly degraded and virtually non-toxic2. In species which do not metabolize the drug, such as mouse and man, the dose-limiting bone marrow and gastro-intestinal toxicity seems to result from persistence of low (10−7 to 10−9 M) plasma levels of methotrexate for many hours after its administration3,4. To counteract this toxicity, 5-formyl tetrahydrofolate, or leucovorin, has been given 12–36 h after high doses of methotrexate, allowing an improvement in the drug's therapeutic index5,6.
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CHABNER, B., JOHNS, D. & BERTINO, J. Enzymatic Cleavage of Methotrexate provides a Method for Prevention of Drug Toxicity. Nature 239, 395–397 (1972). https://doi.org/10.1038/239395b0
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DOI: https://doi.org/10.1038/239395b0
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