Shapiro W R, Young D F, Mehta B M
N Engl J Med. 1975 Jul 24;293(4):161-6. doi: 10.1056/NEJM197507242930402.
The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 times 10-minus 7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 times 10-minus 4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 times 10-minus 5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar puncture, ventricular methotrexate concentration varied considerably from patient to patient despite similar doses. Administration by Ommaya reservoir more reliably produced adequate cerebrospinal fluid distribution than administration by lumbar puncture.
在静脉输注、留置脑室内皮下储液器（Ommaya）或标准腰椎穿刺给药后，对患有脑膜白血病和脑膜癌病的患者，研究了甲氨蝶呤在脑室内和鞘内脑脊液空间中的动力学和分布情况。单次静脉给药后脑室内浓度可忽略不计。在静脉输注期间（每平方米500毫克，持续24小时），脑室内脑脊液浓度升至6×10⁻⁷摩尔/升。通过Ommaya储液器给药，剂量为每平方米6.25毫克，甲氨蝶呤迅速分布于蛛网膜下腔；2×10⁻⁴摩尔/升的脑室内峰值浓度在48小时内呈指数下降。腰椎穿刺脑脊液浓度在注射后4小时达到最大值5×10⁻⁵摩尔/升，然后呈指数下降。腰椎穿刺给药偶尔会导致硬膜外和硬膜下渗漏；即使腰椎穿刺成功，尽管剂量相似，但不同患者的脑室内甲氨蝶呤浓度差异很大。与腰椎穿刺给药相比，通过Ommaya储液器给药能更可靠地使脑脊液充分分布。
