Winick N J, Kamen B A, Streckfuss A, Craig J, McGuirt F, Capizzi R L, Sklar F, Coln D
Cancer Chemother Pharmacol. 1987;20(1):78-80. doi: 10.1007/BF00252965.
Methotrexate (MTX) is a folate analog competitive with reduced folates for cellular transport and metabolism. Since the normal plasma folate concentration is only 10(-8) M, we tested the possibility that there may be a saturable uptake of MTX by proliferating tumor tissue at plasma MTX concentrations of only 10(-7) to 10(-6) M. Patients with advanced malignancies, refractory to accepted therapy, were given low-dose oral MTX (30-60 mg/m2 total dose in four to eight divided doses). Tumor tissue was biopsied 18-24 h after the last oral dose of MTX. The concentrations of MTX and its polyglutamated derivatives were measured in these samples. Forty-eight percent of the drug in the tumor samples was present as a polyglutamated derivative.
甲氨蝶呤（MTX）是一种叶酸类似物，可与还原型叶酸竞争细胞转运和代谢。由于正常血浆叶酸浓度仅为10^(-8) M，我们测试了在血浆MTX浓度仅为10^(-7)至10^(-6) M时，增殖肿瘤组织对MTX可能存在饱和摄取的可能性。对接受的治疗难治的晚期恶性肿瘤患者给予低剂量口服MTX（总剂量30 - 60 mg/m²，分四至八次给药）。在最后一次口服MTX后18 - 24小时对肿瘤组织进行活检。在这些样本中测量MTX及其聚谷氨酸化衍生物的浓度。肿瘤样本中48%的药物以聚谷氨酸化衍生物的形式存在。
