Gutin P H, Green M R, Bleyer W A, Bauer V L, Wiernik P H, Walker M D
Cancer. 1976 Oct;38(4):1529-34. doi: 10.1002/1097-0142(197610)38:4<1529::aid-cncr2820380414>3.0.co;2-e.
A patient with adenocarcinoma of the breast metastatic to the leptomeninges was treated with 10 doses of intrathecal methotrexate (MTX) administered at intervals of 2 days. Following these treatments she developed fever, hypoxemia, and bilateral pulmonary infiltrates without documented pulmonary infection. Autopsy findings were consistent with the pneumonitis that has been associated with intermittent oral, intramuscular, and intravenous MTX therapy. It is suggested that this patient's pulmonary process represented MTX pneumonitis following intrathecal MTX. Cerebrospinal fluid and serum MTX concentrations determined retrospectively on frozen samples reflect an atypically rapid transport of MTX from this patient's cerebrospinal fluid to a slowly decaying systemic pool. Because of this, serum MTX levels probably exceeded 10-8M during the entire 20-day course of therapy, thus exposing the pulmonary parenchyma to significant drug concentrations for a prolonged interval. It is suggested that these unfavorable pharmacokinetics may have contributed to this patient's susceptibility to MTX pneumonitis.
一名乳腺癌转移至软脑膜的患者接受了10剂鞘内注射甲氨蝶呤（MTX）治疗，每2天注射一次。在这些治疗后，她出现发热、低氧血症和双侧肺部浸润，但未记录到肺部感染。尸检结果与口服、肌肉注射和静脉注射MTX间歇治疗相关的肺炎一致。提示该患者的肺部病变为鞘内注射MTX后的MTX肺炎。回顾性测定冷冻样本中的脑脊液和血清MTX浓度，结果显示MTX从该患者的脑脊液向缓慢衰减的全身池转运的速度异常快。因此，在整个20天的治疗过程中，血清MTX水平可能超过10-8M，从而使肺实质在较长时间内暴露于显著的药物浓度下。提示这些不利的药代动力学可能导致该患者易患MTX肺炎。
