Linked Life Data

20600458

Source:http://linkedlifedata.com/resource/pubmed/id/20600458

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-10-11
pubmed:abstractText
The present study defined a simplified physiologically based pharmacokinetic (PBPK) model for acrylonitrile in humans based on in vitro metabolic parameters determined using relevant liver microsomes, coefficients derived in silico, physiological parameters derived from the literature, and a prior previously developed PBPK model in rats. The model basically consists of a chemical absorption compartment, a metabolizing compartment, and a central compartment for acrylonitrile. Evaluation of a previous rat model was performed by comparisons with experimental pharmacokinetic values from blood and urine obtained from rats in vivo after oral treatment with acrylonitrile (30 mg/kg, a no-observed-adverse-effect level) for 14 days. Elimination rates of acrylonitrile in vitro were established using data from rat liver microsomes and from pooled human liver microsomes. Acrylonitrile was expected to be absorbed and cleared rapidly from the body in silico, as was the case for rats confirmed experimentally in vivo with repeated low-dose treatments. These results indicate that the simplified PBPK model for acrylonitrile is useful for a forward dosimetry approach in humans. This model may also be useful for simulating blood concentrations of other related compounds resulting from exposure to low chemical doses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1096-0295
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
252-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Blood concentrations of acrylonitrile in humans after oral administration extrapolated from in vivo rat pharmacokinetics, in vitro human metabolism, and physiologically based pharmacokinetic modeling.
pubmed:affiliation
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't