Linked Life Data

12852442

Source:http://linkedlifedata.com/resource/pubmed/id/12852442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-7-10
pubmed:abstractText
The pulmonary absorption of nine low-molecular-weight (225-430 Da) drugs (atenolol, budesonide, enalaprilat, enalapril, formoterol, losartan, metoprolol, propranolol and terbutaline) and one high-molecular-weight membrane permeability marker compound (FITC-dextran 10000 Da) was investigated using the isolated, perfused and ventilated rat lung (IPL). The relationships between pulmonary transport characteristics, epithelial permeability of Caco-2 cell monolayers and drug physicochemical properties were evaluated using multivariate data analysis. Finally, an in vitro-in vivo correlation was made using in vivo rat lung absorption data. The absorption half-life of the investigated drugs ranged from 2 to 59 min, and the extent of absorption from 21 to 94% in 2 h in the isolated perfused rat lung model. The apparent first-order absorption rate constant in IPL (ka(lung)) was found to correlate to the apparent permeability (P(app)) of Caco-2 cell monolayers (r = 0.87), cLog D(7.4) (r = 0.70), cLog P, and to the molecular polar surface area (%PSA) (r = -0.79) of the drugs. A Partial Least Squares (PLS)-model for prediction of the absorption rate (log ka(lung)) from the descriptors log P(app), %PSA and cLogD(7.4) was found (Q2 = 0.74, R2 = 0.78). Furthermore, a strong in vitro-in vivo correlation (r = 0.98) was found for the in vitro (IPL) drug absorption half-life and the pulmonary absorption half-life obtained in rats in vivo, based on a sub-set of five compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1061-186X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-74
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Drug absorption from the isolated perfused rat lung--correlations with drug physicochemical properties and epithelial permeability.
pubmed:affiliation
Department of Pharmacy, Uppsala University, Box 580, BMC, SE-751 23 Uppsala, Sweden. ann.tronde@astrazeneca.com
pubmed:publicationType
Journal Article, In Vitro