Linked Life Data

9316874

Source:http://linkedlifedata.com/resource/pubmed/id/9316874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-10-17
pubmed:abstractText
The interactions of N4-octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC), a lipophilic derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), were studied in vitro with human blood components. Binding of NOAC incorporated into liposomes to erythrocytes (Ec) was saturated at 63 nmol/10(9) Ec and binding analysis resulted in a weak affinity of 3 x 10(3) liters/mol and 4 x 10(7) binding sites per Ec. The Ec partition coefficient D(Ec) was approximately 4, which demonstrates the high accumulation of NOAC in Ec membranes. The calculated fraction f(b) of drug bound to plasma proteins was 30%. Analysis of serum protein binding of NOAC was done by density gradient ultracentrifugation and agarose gel electrophoresis. Liposomal NOAC was distributed to low-density lipoproteins (LDL) at 36%, to high-density lipoproteins at 21%, to albumin and other proteins at 12% and to very-low-density lipoproteins at 5%. Comparable results were obtained for the analog N4-hexadecyl-1-beta-D-arabinofuranosylcytosine and when the drugs were dissolved in dimethyl sulfoxide. The biodistribution of liposomal NOAC in ICR mice after intravenous application revealed a biphasic blood concentration versus time curve with a distribution half-life t1/2alpha of 23 min and an elimination half-life t1/2beta of 7 h. The drug was distributed mainly into the liver with an organ load of 69% and with an elimination half-life of 8 h. The strong affinity of NOAC to LDL might be exploited for the enhanced uptake of the drug in tumor cells expressing high numbers of LDL receptor molecules.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1572-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Interactions with human blood in vitro and pharmacokinetic properties in mice of liposomal N4-octadecyl-1-beta-D-arabinofuranosylcytosine, a new anticancer drug.
pubmed:affiliation
Department of Pathology, University Hospital, Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't