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Effects of Leucovorin (folinic Acid) in the Methotrexate-treated Rat Brain

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Journal J Vet Med Sci
Date 2018 Apr 3
PMID 29607891
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Abstract

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 k, V, AUC, Cl and t, 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.

References
1.
Zhao R, Goldman I . The proton-coupled folate transporter: physiological and pharmacological roles. Curr Opin Pharmacol. 2014; 13(6):875-80. PMC: 4100332. DOI: 10.1016/j.coph.2013.09.011. View

2.
Ogushi N, Sasaki K, Shimoda M . CAN a P-gp modulator assist in the control of methotrexate concentrations in the rat brain? -inhibitory effects of rhodamine 123, a specific substrate for P-gp, on methotrexate excretion from the rat brain and its optimal route of administration. J Vet Med Sci. 2016; 79(2):320-327. PMC: 5326937. DOI: 10.1292/jvms.16-0315. View

3.
Ghersi-Egea J, Strazielle N . Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus. Microsc Res Tech. 2001; 52(1):83-8. DOI: 10.1002/1097-0029(20010101)52:1<83::AID-JEMT10>3.0.CO;2-N. View

4.
Genoni S, Palus V, Eminaga S, Cherubini G . Safety of intrathecal administration of cytosine arabinoside and methotrexate in dogs and cats. Vet Comp Oncol. 2014; 14(3):331-6. DOI: 10.1111/vco.12109. View

5.
Bleyer W, Poplack D . Prophylaxis and treatment of leukemia in the central nervous system and other sanctuaries. Semin Oncol. 1985; 12(2):131-48. View