Linked Life Data

9311615

Source:http://linkedlifedata.com/resource/pubmed/id/9311615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1997-11-5
pubmed:abstractText
The effect of probenecid (PRB) on factors regulating the hepatic disposition of acetaminophen glucuronide (AG) was investigated in vitro. Potential interactions in metabolism or binding to cytosolic proteins were examined. In the absence of PRB, AG formation in rat hepatic S9 fractions was saturable (V(max) = 2.77 +/- 0.36 nmol/ min/mg protein; K(M) = 18.0 +/- 0.92 mM). PRB significantly decreased V(max), but not K(M), for AG formation, consistent with noncompetitive inhibition. Various models were fit to the AG formation rate vs. acetaminophen (APAP) and PRB concentration data to elucidate the mechanism of inhibition by PRB. A partial noncompetitive inhibition model (K(i) = 1.10 +/- 0.01 mM) described the data best based on model selection criteria. AG did not bind to the cytosolic protein ligandin (glutathione S-transferase A1). These data indicate that PRB is a potent partial noncompetitive inhibitor of acetaminophen glucuronidation in vitro. PRB-associated alterations in AG hepatic disposition in vivo are not due to altered binding of AG to GSTA1 but may be attributed in part to impaired AG formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1017-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
In vitro mechanisms of probenecid-associated alterations in acetaminophen glucuronide hepatic disposition.
pubmed:affiliation
Division of Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, 27599-7360, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S.