A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions

The blood–brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, Kin, is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments ar...

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Bibliographic Details
Published in:Pharmaceutics 2021-05, Vol.13 (5), p.756
Main Authors: Sprowls, Samuel, Saralkar, Pushkar, Arsiwala, Tasneem, Adkins, Christopher, Blethen, Kathryn, Pizzuti, Vincenzo, Shah, Neal, Fladeland, Ross, Lockman, Paul
Format: Article
Language:English
Subjects:
ABC transporters
blood–brain barrier
brain
Glycoproteins
Homeostasis
Kinetics
magnetic-resonance imaging
Permeability
pharmacokinetics
Plasma
preclinical models
Proteins
Review
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Summary:The blood–brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, Kin, is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of Kin for new drug candidates using both intravenous and in situ protocols. Additionally, the single uptake method can be used to determine Kin in heterogeneous pathophysiological conditions such as stroke, brain cancers, and Alzheimer’s disease. In this review, we briefly cover the anatomy and physiology of the BBB, discuss the impact of efflux transporters on solute uptake, and provide an overview of the single-timepoint method for determination of Kin values. Lastly, we compare preclinical Kin experimental results with human parallels.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13050756