Erttmann R, Bielack S, Landbeck G
J Cancer Res Clin Oncol. 1985;109(1):86-8. doi: 10.1007/BF01884261.
7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity. As 7-hydroxy-MTX is a 200 fold less potent dihydrofolic acid reductase inhibitor compared with MTX decreased production of the metabolite may lead to enhanced clinical toxicity which may not be predictable monitoring MTX serum levels alone.
通过高效液相色谱法（HPLC）对7例骨肉瘤患者在连续高剂量甲氨蝶呤（MTX）治疗（12 g/m²）后7-羟基MTX的生成情况进行了测定。结果发现，与辅助化疗方案（COSS 80）的首次高剂量MTX治疗相比，最后一个周期的7-羟基MTX血清值显著降低。此外，在另一例患者中，7-羟基MTX生成的高度降低与严重的临床毒性相关。由于与MTX相比，7-羟基MTX作为二氢叶酸还原酶抑制剂的效力低200倍，该代谢产物生成的减少可能导致临床毒性增强，而仅监测MTX血清水平可能无法预测这种情况。
