7-hydroxy Methotrexate (7-hydroxy MTX) is a phase I metabolite of MTX, which is converted by hepatic aldehyde oxidases.[1] Elimination of 7-hydroxy MTX is associated with the multi-drug transporters Abcc2, Abcc3, and Abcg2 in transgenic mouse models. It and the parent compound rapidly accumulate when all three transporters are absent.[2] Formulations containing methotrexate have been used in the treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions.[3],[4] Various methods have been described to quantify 7-hydroxy MTX levels during cancer therapy to avoid toxicity.[5],[6]
Reference:
[1]. Johns, D.G., Iannotti, A.T., Sartorelli, A.C., et al. The relative toxicites of methotrexate and aminopterin. Biochem. Pharmacol. 15(5), 555-561 (1966).
[2]. Vlaming, M.L.H., van Esch, A., Pala, Z., et al. Abcc2 (Mrp2), Abcc3 (Mrp3), and Abcg2 (Bcrp1) are the main determinants for rapid elimination of methotrexate and its toxic metabolite 7-hydroxymethotrexate in vivo. Mol. Cancer. Ther. 8(12), 3350-3359 (2009).
[3]. Cutolo, M., Sulli, A., Pizzorni, C., et al. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann. Rheum. Dis. 60(8), 729-735 (2001).
[4]. Christin-Maitre, S., Bouchard, P., and Spitz, I.M. Medical termination of pregnancy. N. Engl. J. Med. 342(13), 946-956 (2000).
[5]. 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/MS. Methods in Molecular Biology 213-222 (2016).
[6]. Klapkova, E., Kukacka, J., Kotaska, K., et al. The influence of 7-OH methotrexate metabolite on clinical relevance of methotrexate determination. Clin. Lab. 57(7-8), 599-606 (2011).
[1]. Johns, D.G., Iannotti, A.T., Sartorelli, A.C., et al. The relative toxicites of methotrexate and aminopterin. Biochem. Pharmacol. 15(5), 555-561 (1966).
[2]. Vlaming, M.L.H., van Esch, A., Pala, Z., et al. Abcc2 (Mrp2), Abcc3 (Mrp3), and Abcg2 (Bcrp1) are the main determinants for rapid elimination of methotrexate and its toxic metabolite 7-hydroxymethotrexate in vivo. Mol. Cancer. Ther. 8(12), 3350-3359 (2009).
[3]. Cutolo, M., Sulli, A., Pizzorni, C., et al. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann. Rheum. Dis. 60(8), 729-735 (2001).
[4]. Christin-Maitre, S., Bouchard, P., and Spitz, I.M. Medical termination of pregnancy. N. Engl. J. Med. 342(13), 946-956 (2000).
[5]. 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/MS. Methods in Molecular Biology 213-222 (2016).
[6]. Klapkova, E., Kukacka, J., Kotaska, K., et al. The influence of 7-OH methotrexate metabolite on clinical relevance of methotrexate determination. Clin. Lab. 57(7-8), 599-606 (2011).