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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1995-5-12
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Esters,
http://linkedlifedata.com/resource/pubmed/chemical/GEM91,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/methylphosphonic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0312-5963
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7-16
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7712663-Animals,
pubmed-meshheading:7712663-Antiviral Agents,
pubmed-meshheading:7712663-Base Sequence,
pubmed-meshheading:7712663-Clinical Trials as Topic,
pubmed-meshheading:7712663-Esters,
pubmed-meshheading:7712663-Humans,
pubmed-meshheading:7712663-Molecular Sequence Data,
pubmed-meshheading:7712663-Oligodeoxyribonucleotides, Antisense,
pubmed-meshheading:7712663-Oligonucleotides,
pubmed-meshheading:7712663-Oligonucleotides, Antisense,
pubmed-meshheading:7712663-Organophosphorus Compounds,
pubmed-meshheading:7712663-Thionucleotides,
pubmed-meshheading:7712663-Tissue Distribution
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pubmed:year |
1995
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pubmed:articleTitle |
Pharmacokinetics of antisense oligonucleotides.
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pubmed:affiliation |
Hybridon Inc., Worcester, Massachusetts, USA.
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pubmed:publicationType |
Journal Article,
Review
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