Nelson R W, Frank J T
Am J Hosp Pharm. 1981 Jan;38(1):65-8.
The pharmacokinetics, therapeutic index, neurotoxicities, methods of administration, and dosages of intrathecal methotrexate are reviewed. The intrathecal administration of methotrexate can provide therapeutic concentrations in the cerebrospinal fluid (CSF) without the use of high-dose intravenous methotrexate. Major neurologic complications have been reported to occur in 3--40% of patients following intrathecal methotrexate. The development of neurotoxicity is related to dose, concentration of methotrexate in the CSF, age of the patient, anatomical and physiological abnormalities in the CNS, type of dilutional vehicle, intracranial radiation, and intravenous methotrexate. Substantial evidence is lacking that chemical preservatives and methotrexate breakdown products are risk factors. The use of intrathecal methotrexate is a reasonably safe and effective chemotherapeutic modality when proper administrative techniques are observed.
本文综述了鞘内注射甲氨蝶呤的药代动力学、治疗指数、神经毒性、给药方法及剂量。鞘内注射甲氨蝶呤可在不使用大剂量静脉注射甲氨蝶呤的情况下，使脑脊液（CSF）达到治疗浓度。据报道，鞘内注射甲氨蝶呤后，3%至40%的患者会出现主要神经并发症。神经毒性的发生与剂量、脑脊液中甲氨蝶呤的浓度、患者年龄、中枢神经系统的解剖和生理异常、稀释剂类型、颅内放疗及静脉注射甲氨蝶呤有关。缺乏充分证据表明化学防腐剂和甲氨蝶呤分解产物是危险因素。当遵循适当的给药技术时，鞘内注射甲氨蝶呤是一种相当安全有效的化疗方式。
