Effects of leucovorin (folinic acid) in the methotrexate-treated rat brain

The Journal of Veterinary Medical Science

Kazuaki SASAKI¹  Naofumi OGUSHI² 

[1] Ogushi Animal Hospital, 3-2556-5 Wakasa Tokorozawa-shi, Saitama 359-1151, Japan;The Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan

关键词: blood-brain barrier;    blood-CSF barrier;    folate carrier;    folinic acid;    methotrexate;   

DOI  :  10.1292/jvms.17-0666

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

Folinic acid (FA) is generally administered to patients with CNS tumors in order to treat severe neurological disorders caused by methotrexate (MTX); therefore, we herein examined the effects of the co-administration of FA on MTX concentrations in the rat brain and cerebrospinal fluid (CSF) as well as the pharmacokinetics of MTX. MTX was intravenously or intrathecally administered to rats with or without FA. MTX concentrations were assessed by HPLC. No significant differences were observed in pharmacokinetic parameters, including kel, Vd, AUC, Cltot and t1/2, between the FA-treated and non-treated groups. MTX concentrations were not significantly different in the brain or CSF 6 hr after the intrathecal administration of MTX. However, compare to intravenous administration of MTX, intravenous administration of both FA and MTX significantly decreased MTX concentrations in the brains and CSF. These results suggest that FA inhibits the influx of MTX into the brain and CSF, possibly by competing with folate carriers, but has no effect on its efflux from these regions. Therefore, FA may be administered to CNS tumor patients receiving intrathecal MTX therapy in order to treat the adverse effects of MTX without affecting its concentrations in the brain and CSF.

【 授权许可】

Unknown