Milano G, Thyss A, Renee N, Schneider M, Namer M, Boublil J L, Lalanne C M
Cancer Chemother Pharmacol. 1983;11(1):29-32. doi: 10.1007/BF00257412.
Thirteen patients with cancer being treated with high-dose methotrexate (MTX) chemotherapy (350-5,000 mg/6 h IV were entered in this study. Plasma levels of MTX and 7-OHMTX, its main circulating metabolite, were measured by an HPLC technique. 7-OHMTX appears rapidly in the blood, reaching a maximum 6-12 h after the beginning of treatment. The elimination of 7-OHMTX is slower than that of MTX, but the elimination half-lives (24-48 h) are not significantly different: 25.2 h for 7-OHMTX versus 20.3 h for MTX. In all cases, 24 h after starting infusion plasma levels of 7-OHMTX exceeded those of MTX. There was a positive and significant correlation between the dose administered and peak plasma 7-OHMTX. Finally, 7-OHMTX formation was shown to be relatively stable throughout the treatment.
本研究纳入了13例接受大剂量甲氨蝶呤（MTX）化疗（350 - 5000 mg/6小时静脉注射）的癌症患者。采用高效液相色谱法（HPLC）测定血浆中甲氨蝶呤（MTX）及其主要循环代谢产物7 - 羟基甲氨蝶呤（7 - OHMTX）的水平。7 - OHMTX在血液中迅速出现，在治疗开始后6 - 12小时达到峰值。7 - OHMTX的消除比MTX慢，但消除半衰期（24 - 48小时）无显著差异：7 - OHMTX为25.2小时，MTX为20.3小时。在所有情况下，开始输注24小时后，血浆中7 - OHMTX的水平超过了MTX。给药剂量与血浆7 - OHMTX峰值之间存在显著正相关。最后，在整个治疗过程中，7 - OHMTX的生成显示相对稳定。
