Effect of cyclosporin on distribution of methotrexate into the brain ofrats

Journal of Veterinary Medical Science

Kazuaki SASAKI¹  Naofumi OGUSHI¹  Minoru SHIMODA¹ 

[1] Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183�?8509, Japan

关键词: cyclosporine A;    intrathecal administration;    methotrexate;    P-glycoprotein;   

DOI  :  10.1292/jvms.14-0671

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(13)Cited-By(2)The effect of the antitumor drug, methotrexate (MTX), which is applied to brain tumors,is restricted by the blood-brain barrier (BBB), which is composed of P-glycoprotein (P-gp)and multidrug resistance associated protein (MRP). We, therefore, studied if a potent P-gpand MRP modulator, cyclosporin A (CysA), can modulate the MTX concentration in the ratbrain. If it can, which route is more effective, intravenous or intrathecal? Weintravenously or intrathecally administered MTX to rats with or without CysA. After 6 hr,brains and cerebrospinal fluid (CSF) were sampled, and their MTX concentrations werecompared. Each MTX concentration was determined by high-performance liquid chromatographywith UV detection. CysA had no significant affect on the MTX concentration in the brain orCSF when MTX was intravenously injected. In contrast, when MTX was intrathecallyadministered, CysA had a larger effect on the MTX concentration in the brain than in theCSF. This indicates CysA potentiated the brain MTX concentration when MTX wasintrathecally administered. It is suggested that CysA did not potentiate the distributionof MTX from blood into the brain, but instead potentiated the distribution of MTX from CSFinto the brain. Since chemicals in CSF generally diffuse into the brain easily, CysAprobably inhibited the excretion of MTX from the brain. This could be caused by inhibitionof P-gp or MRP at the BBB. Therefore, CysA can be a useful tool to achieve an appropriateMTX concentration in brain.

【 授权许可】

Unknown