Ashraf Tamima, Robillard Kevin, Chan Gary N Y, Bendayan Reina
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Room 1001, Toronto, ON, Canada, M5S 3M2.
Curr Pharm Des. 2014;20(10):1543-63. doi: 10.2174/13816128113199990464.
Membrane-associated drug transporters are important determinants of antiretroviral drug disposition in the central nervous system during HIV-1 infection. A number of influx and efflux transport proteins expressed at the blood-brain barrier, blood-cerebrospinal fluid barrier and in brain parenchyma cellular compartments (i.e., astrocytes, microglia) have been implicated in the traffic of many antiretroviral drugs into and out of the brain. In particular, members of the ATP-binding cassette membrane associated transporter superfamily and Solute Carrier family are known to be involved in the efflux and/or influx of drugs, respectively. As a result, changes in the functional expression of these transporters can alter the disposition and distribution of drugs in the brain. Moreover, antiretroviral therapy itself and/or pathological events (i.e., inflammation, oxidative stress) associated with viral infection may affect the functional expression of these transporters. This review summarizes recent knowledge on the role of drug transporters in regulating brain antiretroviral drug transport in the context of HIV-1 infection.
膜相关药物转运体是HIV-1感染期间抗逆转录病毒药物在中枢神经系统中处置的重要决定因素。在血脑屏障、血脑脊液屏障以及脑实质细胞区室（即星形胶质细胞、小胶质细胞）表达的许多流入和流出转运蛋白与多种抗逆转录病毒药物进出大脑的转运有关。特别是，已知ATP结合盒膜相关转运体超家族和溶质载体家族的成员分别参与药物的流出和/或流入。因此，这些转运体功能表达的变化可改变药物在大脑中的处置和分布。此外，抗逆转录病毒疗法本身和/或与病毒感染相关的病理事件（即炎症、氧化应激）可能会影响这些转运体的功能表达。本综述总结了关于药物转运体在HIV-1感染背景下调节脑内抗逆转录病毒药物转运作用的最新知识。
