Linked Life Data

1279155

Source:http://linkedlifedata.com/resource/pubmed/id/1279155

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-12-4
pubmed:abstractText
To establish a rationale of designing a drug targeting system using dextran conjugation, the disposition behaviour of dextran itself was investigated in mice. At a high dose (100 mg kg-1), [14C]dextran was retained in the blood circulation for a considerably long period. However, [14C]dextran rapidly disappeared from the plasma and accumulated in the liver (up to 60% of dose in 1 h) after a dose of 1 mg kg-1. Cellular localization of [14C]dextran in the liver following intravenous administration was examined and the contribution of parenchymal cells was demonstrated as well as the case of galactosylated bovine serum albumin (Gal-BSA). Pharmacokinetic analysis based on a physiological model including Michaelis-Menten type uptake mechanisms revealed that the Michaelis constant Km,l of [14C]dextran was 100 times greater than that of Gal-BSA. Coadministration of Gal-BSA delayed the hepatic uptake of [14C]dextran and the simulation based on the physiological model suggested that [14C]dextran was taken up by the same mechanism as Gal-BSA. These results suggested that dextran conjugation of a drug might lead to its undesirable accumulation in the liver at a low dose and an appropriate modification of dextran, such as carboxymethylation, would be required in such cases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3573
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
396-401
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Demonstration of the receptor-mediated hepatic uptake of dextran in mice.
pubmed:affiliation
Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
pubmed:publicationType
Journal Article