Jackson D V, Castle M C, Poplack D G, Bender R A
Cancer Res. 1980 Mar;40(3):722-4.
Adult rhesus monkeys were given 2-mg/sq m i.v. bolus injections of radiochemically pure tritiated vincristine (VCR). Simultaneous specimens of blood and cerebrospinal fluid (CSF) were sampled from 5 min to 72 hr following injection. CSF was obtained from Ommaya reservoirs which had been implanted s.c. in each monkey. VCR and its metabolic and/or decomposition products rapidly entered the CSF producing low concentrations in this fluid; 5 min following injection, the concentration of VCR was 2.3 nM, whereas approximately a 100-fold greater concentration (203.8 nM) was attained in the plasma. Throughout a 3-day period of observation, constant, low levels of VCR and its metabolic and/or decomposition products (2.3 to 5.7 nM) were maintained in the CSF. The principal form of VCR present in the CSF 1 hr or more after i.v. injection was a water-soluble metabolite and/or decomposition product(s). Although the levels achieved in the CSF are unlikely to be lethal to tumor cells, the finding of persistent low concentrations of VCR and its metabolic and/or decomposition products in the CSF indicates prolonged exposure of neural tissue which might result in neurotoxicity, particularly cumulative neurotoxicity following multiple doses of VCR.
给成年恒河猴静脉推注放射化学纯的氚标记长春新碱（VCR），剂量为2毫克/平方米。注射后5分钟至72小时内同时采集血液和脑脊液（CSF）样本。脑脊液通过植入每只猴子皮下的奥马亚贮器获取。VCR及其代谢和/或分解产物迅速进入脑脊液，使该液体中浓度较低；注射后5分钟，VCR浓度为2.3纳摩尔，而血浆中浓度达到约100倍之高（203.8纳摩尔）。在整个3天的观察期内，脑脊液中VCR及其代谢和/或分解产物维持在恒定的低水平（2.3至5.7纳摩尔）。静脉注射1小时或更长时间后，脑脊液中存在的VCR主要形式是水溶性代谢物和/或分解产物。虽然脑脊液中达到的水平不太可能对肿瘤细胞致命，但脑脊液中持续存在低浓度的VCR及其代谢和/或分解产物这一发现表明神经组织长期暴露，这可能导致神经毒性，尤其是多次使用VCR后的累积神经毒性。
