Morikawa N, Mori T, Abe T, Ghoda M, Takeyama M, Hori S
Department of Hospital Pharmacy, Oita Medical University, Japan.
Ann Pharmacother. 1997 Oct;31(10):1153-6. doi: 10.1177/106002809703101007.
To investigate the pharmacokinetics of methotrexate (MTX) in plasma and cerebrospinal fluid (CSF) during osmotic disruption of the blood-brain barrier and the intraarterial administration of combination chemotherapy postoperatively in a patient with glioblastoma.
A 60-year-old Japanese woman with a glioblastoma received two courses of combination intraarterial chemotherapy. In the first course of treatment, 20 mL of mannitol 20%, peplomycin 10 mg, vindesine 2 mg, and MTX 500 mg were administered via the right internal carotid artery, and then via the right vertebral artery. In the second course of treatment, 20 mL of mannitol 20%, peplomycin 15 mg, vindesine 2.5 mg, and MTX 1000 mg were similarly administered. Blood samples and CSF samples from the ventricle and the space left by tumor removal were obtained; the MTX concentrations were measured from these sites by fluorescence polarization immunoassay. The pharmacokinetic parameters of MTX in plasma and CSF were estimated.
The plasma concentration of MTX decreased in a biexponential decay pattern during each course of treatment. CSF concentrations of MTX in the ventricle and in the space left by tumor removal peaked at 2 and 6 hours, respectively, after drug administration and decreased monoexponentially. When the dose of MTX was doubled, the AUC for the plasma MTX concentration increased 2.4-fold and the AUCs for MTX in the ventricle and the space left by tumor removal increased 3.4- and 9.1-fold, respectively. The half-life of MTX in the CSF in the space left by tumor removal exceeded the half-lives of MTX in the plasma and in the ventricular CSF.
The CSF AUCs of MTX in the ventricle and the space left by tumor removal increased markedly and in parallel with the MTX dosage increase during osmotic disruption of the blood-brain barrier and intraarterial combination chemotherapy. Such treatment improves the delivery of chemotherapy agents to the brain.
研究胶质母细胞瘤患者术后血脑屏障渗透性破坏及动脉内联合化疗期间甲氨蝶呤（MTX）在血浆和脑脊液（CSF）中的药代动力学。
一名60岁的日本胶质母细胞瘤女性患者接受了两个疗程的动脉内联合化疗。在第一个疗程中，通过右颈内动脉，然后通过右椎动脉给予20%甘露醇20 mL、培洛霉素10 mg、长春地辛2 mg和MTX 500 mg。在第二个疗程中，同样给予20%甘露醇20 mL、培洛霉素15 mg、长春地辛2.5 mg和MTX 1000 mg。采集血液样本以及来自脑室和肿瘤切除后残留腔隙的脑脊液样本；通过荧光偏振免疫测定法测量这些部位的MTX浓度。估算MTX在血浆和脑脊液中的药代动力学参数。
在每个疗程的治疗期间，MTX的血浆浓度呈双指数衰减模式下降。给药后，脑室和肿瘤切除后残留腔隙中的MTX脑脊液浓度分别在2小时和6小时达到峰值，并呈单指数下降。当MTX剂量加倍时，血浆MTX浓度的AUC增加2.4倍，脑室和肿瘤切除后残留腔隙中MTX的AUC分别增加3.4倍和9.1倍。肿瘤切除后残留腔隙中脑脊液中MTX的半衰期超过血浆和脑室脑脊液中MTX的半衰期。
在血脑屏障渗透性破坏和动脉内联合化疗期间，脑室和肿瘤切除后残留腔隙中MTX的脑脊液AUC显著增加，且与MTX剂量增加平行。这种治疗改善了化疗药物向脑部的递送。
