Evaluation of the Collective Impact of Passive Permeability and Active Transport onIn VivoBlood-Brain Barrier and Gastrointestinal Drug Absorption

2014 ◽  
pp. 263-290
Author(s):  
Donna A. Volpe ◽  
Hong Shen ◽  
Praveen V. Balimane
Keyword(s):  
Active Transport ◽  
Drug Absorption ◽  
Brain Barrier ◽  
Collective Impact ◽  
Passive Permeability

scholarly journals Significance of Lipid Composition in a Blood-Brain Barrier–Mimetic PAMPA Assay

2013 ◽  
Vol 19 (3) ◽  
pp. 437-444 ◽  
Author(s):  
Scott D. Campbell ◽  
Karen J. Regina ◽  
Evan D. Kharasch
Keyword(s):  
Endothelial Cell ◽  
Human Brain ◽  
Blood Brain Barrier ◽  
Lipid Composition ◽  
Brain Barrier ◽  
Brain Lipid ◽  
Passive Permeability ◽  
Whole Brain ◽  
Cell Lipid ◽  
Drug Access

Endothelial cells forming the blood-brain barrier limit drug access into the brain, due to tight junctions, membrane drug transporters, and unique lipid composition. Passive permeability, thought to mediate drug access, is typically tested using porcine whole-brain lipid. However, human endothelial cell lipid composition differs. This investigation evaluated the influence of lipid composition on passive permeability across artificial membranes. Permeability of CNS-active drugs across an immobilized lipid membrane was determined using three lipid models: crude extract from whole pig brain, human brain microvessel lipid, and microvessel lipid plus cholesterol. Lipids were immobilized on polyvinylidene difluoride, forming donor and receiver chambers, in which drug concentrations were measured after 2 h. The log of effective permeability was then calculated using the measured concentrations. Permeability of small, neutral compounds was unaffected by lipid composition. Several structurally diverse drugs were highly permeable in porcine whole-brain lipid but one to two orders of magnitude less permeable across human brain endothelial cell lipid. Inclusion of cholesterol had the greatest influence on bulky amphipathic compounds such as glucuronide conjugates. Lipid composition markedly influences passive permeability. This was most apparent for charged or bulky compounds. These results demonstrate the importance of using species-specific lipid models in passive permeability assays.

scholarly journals Evidence for an active transport of morphine-6-β-d-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier

2003 ◽  
Vol 86 (6) ◽  
pp. 1564-1567 ◽  
Author(s):  
Fanchon Bourasset ◽  
Salvatore Cisternino ◽  
Jamal Temsamani ◽  
Jean-Michel Scherrmann
Keyword(s):  
Blood Brain Barrier ◽  
Active Transport ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain

Active Transport by Insect Malpighian Tubules of Acidic Dyes and of Acylamides

1974 ◽  
Vol 61 (2) ◽  
pp. 357-377 ◽  
Author(s):  
S. H. P. MADDRELL ◽  
B. O. C. GARDINER ◽  
D. E. M. PILCHER ◽  
S. E. REYNOLDS
Keyword(s):  
Active Transport ◽  
Organic Anion ◽  
Indigo Carmine ◽  
Fluid Secretion ◽  
Malpighian Tubules ◽  
Passive Permeability ◽  
Dye Transport ◽  
Tubule Lumen ◽  
Conjugated Compounds ◽  
Tubule Wall

Insect Malpighian tubules carry out active transport of two types of organic anion: acylamides (such as p-aminohippuric acid) and sulphonates (such as indigo carmine and amaranth). There are separate mechanisms for the transport of these two classes of compounds. The degree to which these compounds are concentrated depends critically on the passive permeability of the tubule wall. In the permeable Malpighian tubules of Calliphora, small transported molecules readily escape from the tubule lumen. At low rates of fluid secretion the net rate of dye transport is thereby very much reduced. As a result the rate of dye transport in this insect depends on the rate of fluid secretion, although the processes are not rigidly linked. In the less permeable tubules of Rhodnius and Carausius, dye secretion is not affected by the rate of fluid secretion. The active transport of these two types of compounds is a means of clearing from the haemolymph the conjugated compounds which are the products of detoxication of potentially toxic products of metabolism.

A co-culture-based model of human blood–brain barrier: application to active transport of indinavir and in vivo–in vitro correlation

2002 ◽  
Vol 927 (2) ◽  
pp. 153-167 ◽  
Author(s):  
Isabelle Megard ◽  
Alexia Garrigues ◽  
Stéphane Orlowski ◽  
Sylvie Jorajuria ◽  
Pascal Clayette ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Active Transport ◽  
Human Blood ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Brain-to-blood active transport of β-alanine across the blood-brain barrier

FEBS Letters ◽  
1997 ◽  
Vol 400 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Junko Komura ◽  
Ikumi Tamai ◽  
Mizuho Senmaru ◽  
Tetsuya Terasaki ◽  
Yoshimichi Sai ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Active Transport ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Simulations of Active Transport Across the Blood-Brain Barrier

2020 ◽  
Vol 118 (3) ◽  
pp. 527a
Author(s):  
Christian Jorgensen ◽  
Martin Ulmschneider ◽  
Peter C. Searson
Keyword(s):  
Blood Brain Barrier ◽  
Active Transport ◽  
Brain Barrier ◽  
Blood Brain

Ontogeny of cortical collecting duct sodium transport

1994 ◽  
Vol 267 (1) ◽  
pp. F49-F54 ◽  
Author(s):  
V. M. Vehaskari
Keyword(s):  
Active Transport ◽  
Collecting Duct ◽  
Age Groups ◽  
Cortical Collecting Duct ◽  
Na Transport ◽  
Passive Permeability ◽  
Postnatal Maturation ◽  
Two Stages

The postnatal maturation of Na transport in the rabbit cortical collecting duct (CCD) was investigated. CCD segments from rabbits of three different age groups (3-9 days, 10-15 days, and 22-27 days) were perfused in vitro. Lumen-to-bath 22Na fluxes were 38.5 +/- 4.7, 17.0 +/- 2.9, and 30.2 +/- 4.0 pmol.mm-1.min-1 in the three groups, respectively. The high flux in the youngest group was explained by a high passive flux (28.3 +/- 4.2 pmol.mm-1.min-1) determined in the presence of ouabain; the passive 22Na flux in the two other groups (7.1 +/- 2.6 and 3.1 +/- 2.4 pmol.mm-1.min-1) was not significantly different from previously reported adult values. Ouabain-sensitive 22Na flux, reflecting active transport, was low in the two younger groups (10.3 +/- 2.5 and 9.9 +/- 1.9 pmol.mm-1.min-1), but exhibited a rapid increase to 27.1 +/- 2.6 pmol.mm-1.min-1 by 22-27 days of age. In vivo glucocorticoid pretreatment did not affect the Na transport in any age group. Mineralocorticoid pretreatment for 2 days had no effect in the two younger groups, but increased lumen-to-bath 22Na flux from 30.2 +/- 4.0 to 51.1 +/- 4.3 pmol.mm-1.min-1 in the 22- to 27-day-old group. The findings demonstrate that the maturation of rabbit CCD Na transport occurs in two stages, with the first consisting of a decrease in passive permeability during the first 2 wk of life, followed by an increase in active transport and simultaneous development of mineralocorticoid responsiveness.

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