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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, K(in), is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160855/ https://www.ncbi.nlm.nih.gov/pubmed/34069733 http://dx.doi.org/10.3390/pharmaceutics13050756 |
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author | Sprowls, Samuel A. Saralkar, Pushkar Arsiwala, Tasneem Adkins, Christopher E. Blethen, Kathryn E. Pizzuti, Vincenzo J. Shah, Neal Fladeland, Ross Lockman, Paul R. |
author_facet | Sprowls, Samuel A. Saralkar, Pushkar Arsiwala, Tasneem Adkins, Christopher E. Blethen, Kathryn E. Pizzuti, Vincenzo J. Shah, Neal Fladeland, Ross Lockman, Paul R. |
author_sort | Sprowls, Samuel A. |
collection | PubMed |
description | 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, K(in), is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of K(in) for new drug candidates using both intravenous and in situ protocols. Additionally, the single uptake method can be used to determine K(in) 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 K(in) values. Lastly, we compare preclinical K(in) experimental results with human parallels. |
format | Online Article Text |
id | pubmed-8160855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81608552021-05-29 A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions Sprowls, Samuel A. Saralkar, Pushkar Arsiwala, Tasneem Adkins, Christopher E. Blethen, Kathryn E. Pizzuti, Vincenzo J. Shah, Neal Fladeland, Ross Lockman, Paul R. Pharmaceutics Review 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, K(in), is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of K(in) for new drug candidates using both intravenous and in situ protocols. Additionally, the single uptake method can be used to determine K(in) 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 K(in) values. Lastly, we compare preclinical K(in) experimental results with human parallels. MDPI 2021-05-19 /pmc/articles/PMC8160855/ /pubmed/34069733 http://dx.doi.org/10.3390/pharmaceutics13050756 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Sprowls, Samuel A. Saralkar, Pushkar Arsiwala, Tasneem Adkins, Christopher E. Blethen, Kathryn E. Pizzuti, Vincenzo J. Shah, Neal Fladeland, Ross Lockman, Paul R. A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions |
title | A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions |
title_full | A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions |
title_fullStr | A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions |
title_full_unstemmed | A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions |
title_short | A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions |
title_sort | review of mathematics determining solute uptake at the blood–brain barrier in normal and pathological conditions |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160855/ https://www.ncbi.nlm.nih.gov/pubmed/34069733 http://dx.doi.org/10.3390/pharmaceutics13050756 |
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