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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-17
pubmed:abstractText
In situ and in vitro intestinal absorption in the rat ileum was systematically studied and mechanistically quantified in terms of permeability coefficients (P) of a series of [(3)H]steroids as model transcellular permeants, [(3)H]taurocholate utilizing the active membrane transport systems to define the aqueous boundary layer (ABL), and [(14)C]urea and [(14)C]mannitol as pore-hindered paracellular diffusants. In situ single-pass perfusion experiments were performed in isolated ileal segments and blood samples were collected from the cannulated mesenteric vein. For the in vitro experiments, an excised, serosal and muscular layer-removed, ileal tissue was mounted in the Ussing chamber diffusion cells. In situ and in vitro P values versus logarithm of the partition coefficient in n-octanol/water (log K) of the steroids were characterized by a sigmoidal-shaped curve in which plateau values were attained for the highly lipophilic steroids with log K greater, similar 2.5. The in situ and in vitro transport barriers in series were viewed as ABL/mucosal epithelium and ABL/mucosal epithelium/submucosal tissue, respectively. Within this framework and the use of experimental strategies and theoretical reasoning, the transport barriers of the steroids were quantitatively delineated and the rate-determining barriers identified. In the plateau region, the analyses indicate that the in situ absorption of the lipophilic steroids was essentially ABL controlled, whereas the in vitro absorption was about equally controlled by diffusion across the ABL and submucosal tissue. The in situ and in vitro pore radii of the paracellular route were 7.2 and 9.2 A, respectively, and the difference was likely the result of perturbation of the tight junctions during the in vitro preparation of the ileal tissue.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:344-359, 2003
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
344-59
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12532384-Algorithms, pubmed-meshheading:12532384-Animals, pubmed-meshheading:12532384-Diffusion Chambers, Culture, pubmed-meshheading:12532384-Epithelium, pubmed-meshheading:12532384-Ileum, pubmed-meshheading:12532384-Indicators and Reagents, pubmed-meshheading:12532384-Intestinal Absorption, pubmed-meshheading:12532384-Kinetics, pubmed-meshheading:12532384-Male, pubmed-meshheading:12532384-Mannitol, pubmed-meshheading:12532384-Mesenteric Veins, pubmed-meshheading:12532384-Models, Biological, pubmed-meshheading:12532384-Perfusion, pubmed-meshheading:12532384-Permeability, pubmed-meshheading:12532384-Porosity, pubmed-meshheading:12532384-Rats, pubmed-meshheading:12532384-Rats, Sprague-Dawley, pubmed-meshheading:12532384-Steroids, pubmed-meshheading:12532384-Taurocholic Acid, pubmed-meshheading:12532384-Urea
pubmed:year
2003
pubmed:articleTitle
A systematic examination of the in vitro Ussing chamber and the in situ single-pass perfusion model systems in rat ileum permeation of model solutes.
pubmed:affiliation
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, Utah 84112, USA.
pubmed:publicationType
Journal Article, In Vitro