Linked Life Data

17344354

Source:http://linkedlifedata.com/resource/pubmed/id/17344354

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-5-23
pubmed:abstractText
The purpose of the present study was to investigate the role of multidrug resistance-associated protein 4 (MRP4) in the tubular secretion of cephalosporin antibiotics. Most of the injectable cephalosporins have an inhibitory effect on the ATP-dependent uptake of [(3)H]dehydroepiandrosterone sulfate by membrane vesicles expressing hMRP4, whereas cephaloridine, cefsulodin, and cefepime do not. Aminocephalosporins have a weak inhibitory effect. Significant ATP-dependent transport of ceftizoxime (K(m), 18 microM), cefazolin (K(m), 80 microM), cefotaxime, and cefmetazole has been observed only in the membrane vesicles expressing hMRP4. Ceftizoxime and cefazolin were given by a constant intravenous infusion to wild-type and Mrp4(-/-) mice. The steady-state plasma concentrations of ceftizoxime and cefazolin were unchanged in Mrp4(-)(/)(-) mice. The urinary recovery of ceftizoxime was significantly reduced in Mrp4(-/-) mice, whereas it was unchanged for cefazolin. The kidney-to-plasma concentration ratio of ceftizoxime and cefazolin was increased 2.0- and 2.7-fold in Mrp4(-/-) mice, respectively; thus, the renal clearance with regard to the kidney concentration was reduced in Mrp4(-/-) mice, to 7.5 and 34% of the corresponding control values, respectively. These results suggest that Mrp4 is involved in the tubular secretion of ceftizoxime and cefazolin, in concert with basolateral uptake transporters.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1591-7
pubmed:dateRevised
2009-2-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Involvement of MRP4 (ABCC4) in the luminal efflux of ceftizoxime and cefazolin in the kidney.
pubmed:affiliation
Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural