The Journal of Veterinary Medical Science

19 Folinic acid (FA) is generally administered to patients with CNS tumors in order to 20 treat severe neurological disorders caused by methotrexate (MTX); therefore, we herein 21 examined the effects of the co-administration of FA on MTX concentrations in the rat 22 brain and cerebrospinal fluid (CSF) as well as the pharmacokinetics of MTX. MTX was 23 intravenously or intrathecally administered to rats with or without FA. MTX 24 concentrations were assessed by HPLC. No significant differences were observed in 25 pharmacokinetic parameters, including kel, Vd, AUC, Cltot, and t1/2, between the FA26 treated and non-treated groups. MTX concentrations were not significantly different in 27 the brain or CSF 6 hrs after the intrathecal administration of MTX. However, compare 28 to intravenous administration of MTX, intravenous administration of both FA and MTX 29 significantly decreased MTX concentrations in the brains and CSF. These results 30 suggest that FA inhibits the influx of MTX into the brain and CSF, possibly by 31 competing with folate carriers, but has no effect on its efflux from these regions. 32 Therefore, FA may be administered to CNS tumor patients receiving intrathecal MTX 33 therapy in order to treat the adverse effects of MTX without affecting its concentrations 34 in the brain and CSF. 35