脑室给甲氨蝶呤治疗脑肿瘤患者脑脊液中的药代动力学

Pharmacokinetics of methotrexate in cerebrospinal fluid after intracerebroventricular chemotherapy to a patient with recurrent intracranial germioma

对脑肿瘤病人脑室内注射 5mg甲氨蝶呤(MTX) 3次后 ,脑脊液 (CSF)中MTX呈二室开放动力学特点 .主要动力学参数 :t1/ 2α=3h ;t1/ 2 β=4 8.2h ;Vc =15.6mL ;AUC =6365mg·h·L- 1;Cl =0 .32 4mL·h- 1.给药后 4 8h血药浓度很低 ,峰值 ( 4h)时仅有 0 .7mg·L- 1.对MTX经脑室给药CSF药物浓度高 ,维持时间久 。

Blood brain barrier and blood cerebrospinal fluid(CSF) barrier are almost totally impermeable to non lipid soluble drugs including methotrexate(MTX). Therefore, MTX would have no effect at all on the brain when it is introduced into the blood. However, it could have excellent effects on the brain by injecting into the CSF. In this article, the pharmacokinetics of MTX in CSF was analyzed after injecting 5 mg MTX to the right cerebral ventricle of a patient with recurrent intracranial germioma, which disseminated along ependyma to ventricular system. Concentration of MTX in CSF was dramatically high, from 990 mg·L -1 (0.5 h) to 80 mg·L -1 (48 h). It was determined by phosphorimetric method. The mathema tic expression of MTX concentration in CSF is: c mg·L -1 =245.3 e -0.2304 t +76.22 e -0.01438 t Some main pharmacokinetic parameters were calculated as: t 1/2α =3 h; t 1/2β =48.2 h; Vc=15.55 mL; AUC=6365 mg·h·L -1 ; Cl=0.324 mL·h -1 . At the same time, blood drug concentration of MTX was very low, and nearly in the same level(below 1 mg·L -1 ). This article also discussed the theory and prospect of chemotherapy by intraventricular injection.