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• W1964184604 abstract "P-glycoprotein (Pgp) in the blood–brain barrier limits the brain's uptake of many anticancer drugs. We have investigated whether the Pgp inhibitors cyclosporin A, valspodar (PSC833) and elacridar (GF120918) increase the accumulation of docetaxel in the brain. Pgp knockout mice served as a reference model for the complete absence or complete inhibition of Pgp. Plasma and tissues were analysed by high-performance liquid chromatography. Cyclosporin A, valspodar and elacridar significantly increased the brain concentrations of docetaxel in wild-type mice to 38%, 56% and 59%, respectively, of those achieved in Pgp knockout mice. Valspodar and cyclosporin A also increased the docetaxel concentration in plasma and other tissues by 2- and 3-fold, whereas elacridar did not change the clearance. All three inhibitors therefore inhibit Pgp in the blood–brain barrier. Elacridar increases the accumulation of docetaxel in the brain without significant effects on systemic exposure. Further clinical tests with this latter combination are warranted." @default.
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• W1964184604 date "2004-05-01" @default.
• W1964184604 modified "2023-10-12" @default.
• W1964184604 title "Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoprotein" @default.
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• W1964184604 doi "https://doi.org/10.1016/j.ejca.2004.01.024" @default.
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