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- W4302278166 abstract "The blood-brain barrier (BBB) expresses a high abundance of transporters, particularly P-glycoprotein (P-gp), that regulate endogenous and exogenous molecule uptake and removal of waste. This review discusses key drug metabolism and pharmacokinetic considerations for the efflux transporter P-gp at the BBB in drug discovery and development. We highlight the differences in P-gp expression and protein levels across species but the limited observations of species-specific substrates. Given the impact of age and disease on BBB biology, we summarise the modulation of P-gp for several neurological disorders and ageing and exemplify several disease-specific hurdles or opportunities for drug exposure in the brain. Furthermore, the review includes observations of CNS-related drug-drug interactions due to the inhibition or induction of P-gp at the BBB in animal studies and humans and the need for continued evaluation especially for compounds with a narrow therapeutic window. This review focusses primarily on small molecules but also considers the impact of new chemical entities, particularly beyond Ro5 molecules and their potential to be recognised as P-gp substrates as well as advanced drug delivery systems which offer an alternative approach to achieve and sustain central nervous system exposure." @default.
- W4302278166 created "2022-10-06" @default.
- W4302278166 creator A5040710050 @default.
- W4302278166 creator A5058332529 @default.
- W4302278166 creator A5064652511 @default.
- W4302278166 date "2022-10-17" @default.
- W4302278166 modified "2023-10-12" @default.
- W4302278166 title "The role of the efflux transporter, P‐glycoprotein, at the blood–brain barrier in drug discovery" @default.
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- W4302278166 doi "https://doi.org/10.1002/bdd.2331" @default.
- W4302278166 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36198662" @default.
- W4302278166 hasPublicationYear "2022" @default.
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