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- W2559361629 abstract "Although methotrexate (MTX) is mainly transported by reduced folate carrier, P-gp and MRP1 may also be involved in its transport. In our previous study, a potent P-gp and MRP1 modulator, Cyclosporine A, potentiated MTX concentration in rat brain. Since it is important for MTX therapy for brain tumor to clarify which transporter is dominant, we herein determined whether the specific P-gp substrate, rhodamine123 (Rho123), potentiates the transport and retention of MTX in the brain. Rho123 was injected intravenously or intrathecally into rats immediately after injection of MTX. 6 or 12 hr after the MTX injection, brains were isolated just after the sampling of cerebrospinal fluid (CSF). Blood was also collected intermittently. MTX concentrations were determined in plasma, CSF and the brain using high-performance liquid chromatography with UV detection. When MTX was intravenously injected, Rho123 didn’t affect MTX concentrations in the brain. However, Rho123 resulted in significantly higher MTX concentrations in the brain at 12 hr after injection when MTX was intrathecally injected. It is suggested that Rho123 inhibits the excretion of MTX from the brain, but does not potentiate its distribution from the blood into the brain. This reveals that P-gp can be one of the major transporters of MTX in rat brain. Therefore, treatments with P-gp modulators may contribute to intrathecal MTX therapy for brain tumor. Since plasma concentration-time curves of MTX were not affected by Rho123, treatments with P-gp modulators may not potentiate the adverse effects of MTX." @default.
- W2559361629 created "2016-12-08" @default.
- W2559361629 creator A5037163338 @default.
- W2559361629 creator A5049620547 @default.
- W2559361629 creator A5067307105 @default.
- W2559361629 date "2017-01-01" @default.
- W2559361629 modified "2023-10-02" @default.
- W2559361629 title "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" @default.
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- W2559361629 doi "https://doi.org/10.1292/jvms.16-0315" @default.
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