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JOURNAL ARTICLE
REVIEW
Impact of transporters and enzymes from blood-cerebrospinal fluid barrier and brain parenchyma on CNS drug uptake.
Expert Opinion on Drug Metabolism & Toxicology 2018 September
INTRODUCTION: In parallel with the blood-brain barrier (BBB), transporters and enzymes on the blood-cerebrospinal fluid barrier (BCSFB) serve as the first barrier for drug brain uptake. In addition, their expressions on brain parenchyma are considered as the secondary barrier for central nervous system (CNS) drug delivery. Currently, a lack of information on transporters and enzymes expressed on both BCSFB and brain parenchyma is the major cause of failure in CNS drug development. Areas covered: Transporters and enzymes expressed on BCSFB and brain parenchyma and their impact on drug brain uptake were highlighted and compared with that on BBB. Expert opinion: Based on the nature of transporters expressed on BCSFB and the brain parenchyma, the design of CNS therapeutics with chemical structures similar to the substrates of nutrients and hormones transporters could facilitate their CSF and brain parenchyma uptake . Moreover, drugs in systemic circulation could undergo further metabolism at BCSFB and brain parenchyma leading to failure in CNS drug delivery. Impact of the altered expressions and functions of transporters and enzymes on BCSFB and brain parenchyma in different species or disease conditions on CNS drug brain uptake shall be further evaluated using relevant in vitro cell models and pharmacokinetics modeling.
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