Linked Life Data

14985145

Source:http://linkedlifedata.com/resource/pubmed/id/14985145

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-26
pubmed:abstractText
1. Recombinantly expressed human cytochromes P450 (rhCYPs) have been underused for the prediction of human drug clearance (CL). 2. Differences in intrinsic activity (per unit CYP) between rhCYP and human liver enzymes complicate the issue and these discrepancies have not been investigated systematically. We define intersystem extrapolation factors (ISEFs) that allow the use of rhCYP data for the in vitro-in vivo extrapolation of human drug CL and the variance that is associated with interindividual variation of CYP abundance due to genetic and environmental effects. 3. A large database (n = 451) of metabolic stability data has been compiled and used to derive ISEFs for the most commonly used expression systems and CYP enzymes. 4. Statistical models were constructed for the ISEFs to determine major covariates in order to optimize experimental design to increase prediction accuracy. 5. Suggestions have been made for the conduct of future studies using rhCYP to predict human drug clearance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-78
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors.
pubmed:affiliation
Molecular Pharmacology and Pharmacogenetics, Clinical Sciences Division (South), University of Sheffield, The Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't