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- W1998989929 abstract "The central nervous system (CNS), efficiently isolated from the systemic circulation by the blood-brain barrier (BBB), represents a challenging therapeutic target. For CNS-targeted agents, augmenting brain exposure by increasing blood drug concentrations often is prohibited by systemic toxicity. Therefore, a means for selectively increasing brain exposure, while minimizing systemic exposure, would be desirable. Limited evidence has indicated that nasally-administered compounds can penetrate into brain, although the selectivity of this approach is unclear. This study demonstrated a distinct, but compound-specific, advantage of the nasal administration route in conferring selective CNS delivery (defined as a brain exposure advantage; BEA). Brain and systemic concentrations of three P-glycoprotein-inhibiting agents were evaluated following single nasal or systemic doses to mice, and the influence of administration route on brain exposure (absolute BEA) and on brain-to-blood partitioning (relative BEA) was calculated. Relative and absolute BEA differed markedly among rifampin, quinidine, and GF120918, with relative BEA ranging between 1.53- and 809-fold and absolute BEA between 0.114- and 9.19-fold. Although substantial increases in brain exposure and partitioning in conjunction with nasal administration were demonstrated, the utility of this approach may be limited by inability to deliver a therapeutically relevant mass of drug to the brain." @default.
- W1998989929 created "2016-06-24" @default.
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- W1998989929 date "2010-07-01" @default.
- W1998989929 modified "2023-09-25" @default.
- W1998989929 title "Examination of the Ability of the Nasal Administration Route to Confer a Brain Exposure Advantage for Three Chemical Inhibitors of P-Glycoprotein" @default.
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- W1998989929 doi "https://doi.org/10.1002/jps.22070" @default.
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