Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-5-12
pubmed:abstractText
Antisense oligonucleotides are promising therapeutic agents for the treatment of life-threatening diseases. Intravenous injection of phosphodiester oligonucleotide analogue (P-oligonucleotide) in monkeys shows that the oligonucleotide is degraded rapidly in the plasma with a half-life of about 5 minutes. Administration of a single dose of the phosphorothioate (S-oligonucleotide) in animals by the intravenous route reveals biphasic plasma elimination. An initial short half-life (0.53 to 0.83 hours) represents distribution out of the plasma compartment and a second long half-life (35 to 50 hours) represents elimination from the body. This elimination half-life was similar when the oligonucleotide was administered subcutaneously. In contrast, methylphosphonate oligonucleotides have an elimination half-life of 17 minutes in mice. S-Oligonucleotide was distributed into most of organs of rats and mice. Liver and kidney were the 2 organs with highest uptake of the oligonucleotide. The S-oligonucleotide was primarily excreted in urine. Up to 30% was excreted in the first 24 hours. Repeated daily intravenous injections of a 25-mer S-oligonucleotide into rats showed that the concentrations in the plasma are at steady-state during the 8 days' administration. The data represented here support the potential utility of phosphorothioate and methylphosphonate oligonucleotides as therapeutic agents in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0312-5963
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-16
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Pharmacokinetics of antisense oligonucleotides.
pubmed:affiliation
Hybridon Inc., Worcester, Massachusetts, USA.
pubmed:publicationType
Journal Article, Review