7-hydroxy Methotrexate (7-hydroxy MTX) is the major metabolite of the folic acid derivative MTX .1 It is formed by the 7-oxidation of MTX by hepatic aldehyde oxidases. Unlike MTX, 7-hydroxy MTX does not inhibit thymidylate synthase in isolated human acute myeloid and acute lymphoblastic leukemia cells.2 7-hydroxy MTX has a maximum tolerated dose of 0.1 g/kg, which is 30- to 50-fold lower than MTX, in rats.3 Serum levels of 7-hydroxy MTX have been used as a marker of MTX toxicity during chemotherapy.4,5
1.Johns, D.G., Iannotti, A.T., Sartorelli, A.C., et al.The relative toxicites of methotrexate and aminopterinBiochem. Pharmacol.15(5)555-561(1966) 2.Lingg, R.M., Hempel, G., Rots, M.G., et al.Effects and interaction of 7-hydroxy methotrexate and methotrexate in leukaemic cells ex vivo measured by the thymidylate synthase inhibition assayCancer Chemother. Pharmacol.56(3)322-327(2005) 3.Fuskev?g, O.M., Kristiansen, C., Lindal, S., et al.Maximum tolerated doses of methotrexate and 7-hydroxy-methotrexate in a model of acute toxicity in ratsCancer Chemother. Pharmacol.46(1)69-73(2000) 4.Schofield, R.C., Ramanathan, L.V., Murata, K., et al.Development of an assay for methotrexate and its metabolites 7-hydroxy methotrexate and DAMPA in serum by LC-MS/MSMethods in Molecular Biology213-222(2016) 5.Klapkova, E., Kukacka, J., Kotaska, K., et al.The influence of 7-OH methotrexate metabolite on clinical relevance of methotrexate determinationClin. Lab.57(7-8)599-606(2011)

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