Morikawa N, Mori T, Kawashima H, Takeyama M, Hori S
Department of Clinical Pharmacy, Oita Medical University, Japan.
Biol Pharm Bull. 2000 Jun;23(6):774-7. doi: 10.1248/bpb.23.774.
This paper investigates the post-surgical pharmacokinetics of methotrexate (MTX) in the plasma, the cerebrospinal fluids (CSF), and the spaces created by tumor removal (STR) in patients with glioblastoma, during hyperosmotic disruption of the blood brain barrier (HODBBB) and intra-arterial chemotherapy with MTX. Eight Japanese patients with glioblastoma, three with open STRs and five with closed STRs, received a total of thirteen courses of HODBBB and intra-arterial combination chemotherapy with MTX. The patients were initially administered mannitol, then the anticancer drugs were infused into the carotid artery. Samples of blood and CSF from the STRs were obtained. MTX concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of MTX in plasma and CSF were estimated. The plasma concentrations of MTX peaked at the end of drug infusion, and then decayed bi-exponentially during the remainder of the treatment period. The CSF concentration of MTX in the STR peaked 2 h after drug administration, then mono-exponentially decreased. The area under the concentration-time curve (AUC) for plasma and CSF MTX concentrations increased in parallel with the MTX dose. In patients with open STRs, the mean AUC of MTX in CSF was 4.44% of that found in plasma, while in patients with closed STRs, the mean was 61.2% of that found in plasma. In the latter group, the MTX administered using HODBBB and intra-arterial chemotherapy was maintained in the STRs for long periods.
本文研究了胶质母细胞瘤患者在血脑屏障高渗破坏（HODBBB）和甲氨蝶呤（MTX）动脉内化疗期间，MTX在血浆、脑脊液（CSF）以及肿瘤切除后形成的腔隙（STR）中的术后药代动力学。8例日本胶质母细胞瘤患者，3例为开放型STR，5例为封闭型STR，共接受了13个疗程的HODBBB和MTX动脉内联合化疗。患者先静脉注射甘露醇，然后将抗癌药物注入颈动脉。采集STR处的血液和CSF样本。采用荧光偏振免疫分析法测定MTX浓度，并估算MTX在血浆和CSF中的药代动力学参数。MTX血浆浓度在药物输注结束时达到峰值，然后在治疗期的剩余时间内呈双指数衰减。STR处CSF中MTX浓度在给药后2小时达到峰值，然后呈单指数下降。血浆和CSF中MTX浓度-时间曲线下面积（AUC）与MTX剂量平行增加。开放型STR患者CSF中MTX的平均AUC为血浆中的4.44%，而封闭型STR患者平均为血浆中的61.2%。在后一组中，使用HODBBB和动脉内化疗给予的MTX在STR中长时间维持。
