Linked Life Data

14659483

Source:http://linkedlifedata.com/resource/pubmed/id/14659483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-5
pubmed:dateCreated
2003-12-8
pubmed:abstractText
Iso-pH mapping unstirred parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, P(o), the unstirred water layer (UWL) permeability, P(u), and the apparent pK(a) (pK(a)(flux)) were determined from the pH dependence of logP(e). The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases and ampholytes. The average thickness of the unstirred water layer on each side of the membrane was estimated to be nearly 2000 microm, somewhat larger than that found in Caco-2 permeability assays (unstirred). Since the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g. pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially-selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log P(e)-pH plots, a method to improve the selection of the assay pH, called pK(a)(flux)-optimized design (pOD-PAMPA), was described and tested. From an optimally-selected assay pH, it is possible to estimate P(o), as well as the entire membrane permeability-pH profile.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0928-0987
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
393-402
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
PAMPA--a drug absorption in vitro model. 5. Unstirred water layer in iso-pH mapping assays and pKa(flux)--optimized design (pOD-PAMPA).
pubmed:affiliation
pION INC., 5 Constitution Way, Woburn, MA 01801, USA.
pubmed:publicationType
Journal Article