Linked Life Data

8746777

Source:http://linkedlifedata.com/resource/pubmed/id/8746777

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-1-15
pubmed:abstractText
To clarify the renal disposition characteristics of oligonucleotides at the organ level, the renal handling of model end-capped oligonucleotides, 3'-methoxyethylamine 5'-biotin-decathymidylic acid containing phosphoramidate modifications at 3'- and 5'-terminal internucleoside linkages (T10) and its phosphorothioate (Ts10), were studied in the perfused rat kidney. In a single-pass indicator dilution experiment, venous outflow and urinary excretion patterns and tissue accumulation of radiolabeled oligonucleotides were evaluated under filtering or nonfiltering conditions. No significant binding to bovine serum albumin (BSA) in the perfusate was observed for T10, whereas more than 90% of Ts10 bound to BSA. The steady-state distribution volume of T10 calculated from the venous outflow pattern was larger than that of inulin, which corresponds to the extracellular volume of the kidney, whereas the distribution volume of Ts10 was larger than that of BSA (the intravascular volume). These results suggested their interaction with the vascular wall. Rapid urinary excretion was observed for T10, similar to inulin used as a marker of golmerular filtration rate. On the other hand, urinary excretion of Ts10 was greatly restricted due to its high binding ability (> 90%) to BSA in the perfusate. A significant amount of T10 and Ts10 was accumulated in the kidney (T10, 1.8% of injected dose; Ts10, 1.3%) compared with inulin (0.2%) and BSA (< 0.1%). The accumulation of these oligonucleotides was ascribed to both tubular reabsorption and uptake from the capillary side. In addition, the uptake of T10 from the capillary side was significantly inhibited by simultaneous injection of dextran sulfate, suggesting that the oligonucleotide was taken up as an anionic molecule. These findings will be useful information for the development of delivery systems for antisense oligonucleotides.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1050-5261
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
279-87
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Renal disposition characteristics of oligonucleotides modified at terminal linkages in the perfused rat kidney.
pubmed:affiliation
Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
pubmed:publicationType
Journal Article, In Vitro