Linked Life Data

15072798

Source:http://linkedlifedata.com/resource/pubmed/id/15072798

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-4-9
pubmed:abstractText
Presently, the Caco-2 cell culture model is widely used during drug discovery and development as a predictive tool for the oral absorption of drug candidates. For transport experiments in the Caco-2 system, HBSS-like buffered salt solutions are commonly used, although different shortcomings have been associated with the use of these buffers. In this paper, we investigated the effect of using fasted state simulated intestinal fluid (FaSSIF) as potential biorelevant medium for the drug permeability estimation across Caco-2 monolayers. The transport characteristics of 19 model compounds were determined in the Caco-2 cell culture model in the presence of FaSSIF as compared to classic transport medium. A sigmoidal relation was obtained when the estimated P(app), s of the apical to basolateral transport were plotted versus the reported values of the fraction absorbed in man. Although no effect of FaSSIF as compared to classic transport medium (TM) was observed on the total predictability of the model, an impact was demonstrated (1) on the bi-directional transport of actively transported drugs (including talinolol, digoxin and doxorubicin), (2) on recovery and (3) on the solubility and permeability estimation of poorly water-soluble drugs. The observed differences may be attributed to a P-gp inhibitory effect of sodium taurocholate (NaTC), micellar encapsulation by the NaTC/lecithin mixed micelles and/or an increase of the solubility of lipophilic drugs. As the experimental conditions should mimic the physiological in vivo conditions, the use of FaSSIF as medium during Caco-2 experiments may improve the biorelevance of the model.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0378-5173
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-32
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effect of simulated intestinal fluid on drug permeability estimation across Caco-2 monolayers.
pubmed:affiliation
Biopharmaceutics & Drug Delivery, Lilly Development Centre, 11 rue Granbonpré, 1348 Mont-Saint-Guibert, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't