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• W2323960661 abstract "Objective: In AIDS, early suppression of the viral load in the central nervous system is critical for the efficacy of antiretroviral therapy, in order to prevent the emergence of a reservoir of resistant strains of virus, and brain impairment in late stages of the infection. The blood–cerebrospinal fluid (CSF) interface (i.e. the choroidal epithelium) constitutes the most direct route to reach the ventricular meningeal and perivascular infected macrophages, and may modulate the cerebral biodisposition of antiretroviral drugs through various transport systems. Our aim was to address nucleoside drug transfer specifically across the blood–CSF interface, and identify the possible mechanisms involved in their transport. Methods: Drug influx and efflux were measured using an in vitro cellular model that reproduces the barrier and transport properties of the blood–CSF interface in vivo. Transport mechanisms were investigated by competition studies. Results: The CSF influx rate of zidovudine was the highest, although moderate, followed by that of stavudine. The permeability coefficients of the other drugs tested were low. Zidovudine influx into the CSF is independent of thymidine transport systems, and more importantly is limited by an efflux mechanism. This efflux involves an apical (CSF-facing) carrier belonging to the solute carrier (Slc) 22 family of organic anion transporters, and can be inhibited by a therapeutic concentration of benzbromarone. Conclusions: The demonstration and characterization of this efflux mechanism is the basis for the development of specific inhibitory agents in view to increase the delivery of antiretroviral nucleoside analogs to the brain." @default.
• W2323960661 created "2016-06-24" @default.
• W2323960661 creator A5060084331 @default.
• W2323960661 creator A5062096867 @default.
• W2323960661 creator A5081078486 @default.
• W2323960661 date "2003-07-01" @default.
• W2323960661 modified "2023-10-03" @default.
• W2323960661 title "Choroid plexus controls brain availability of anti-HIV nucleoside analogs via pharmacologically inhibitable organic anion transporters" @default.
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• W2323960661 doi "https://doi.org/10.1097/00002030-200307040-00008" @default.
• W2323960661 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12824785" @default.
• W2323960661 hasPublicationYear "2003" @default.
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