Evidence map›Paper›PMID 10468036›Full record

ArticlePharmaceutical research1999

Pharmacokinetics and tissue disposition in monkeys of an antisense oligonucleotide inhibitor of Ha-ras encapsulated in stealth liposomes.

R Z Yu, R S Geary, J M Leeds, T Watanabe, J R Fitchett, J E Matson, R Mehta, G R Hardee, M V Templin, K Huang and 8 more

Abstract read
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Article in Pharmaceutical research, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 46 citations in OpenAlex.

  1. Refilling drug delivery depots through the blood.Proceedings of the National Academy of Sciences of the United States of America · 2014
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

R Z YuIsis Pharmaceuticals, Inc., Carlsbad, California 92008, USA. ryu@isisph.com
R S Geary
J M Leeds
T Watanabe
J R Fitchett
J E Matson
R Mehta
G R Hardee
M V Templin
K Huang
M S Newman
Y Quinn
P Uster
G Zhu
P K Working
M Horner
J Nelson
A A Levin
Ionis Pharmaceuticals (United States) · USSierra BioMedical (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThis study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated).

methodsEncapsulated or unencapsulated ISIS 2503 was administered to rhesus monkeys by intravenous infusion. The concentrations of ISIS 2503 and metabolites in blood, plasma, and tissue samples were determined by capillary gel electrophoresis.

resultsPlasma concentrations of encapsulated ISIS 2503 decreased mono-exponentially after infusion with a mean half-life of 57.8 hours. In contrast, the concentration of unencapsulated ISIS 2503 in plasma decreased rapidly with a mean half-life of 1.07 hours. Both encapsulated and unencapsulated ISIS 2503 distributed widely into tissues. Encapsulated ISIS 2503 distributed primarily to the reticulo-endothelial system and there were few metabolites observed. In contrast, unencapsulated ISIS 2503 distributed rapidly to tissue with highest concentration seen in kidney and liver. Nuclease-mediated metabolism was extensive for unencapsulated oligonucleotide in plasma and tissues.

conclusionsThe data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.

Indexed as

AnimalsBlood ProteinsCapsulesDrug Delivery SystemsFemaleGene Expression RegulationHalf-LifeKineticsLiposomesMacaca mulattaMaleMetabolic Clearance RateOligonucleotides, AntisensePhosphorothioate Oligonucleotidesras ProteinsTissue DistributionBlood ProteinsCapsulesISIS 2503LiposomesOligonucleotides, AntisensePhosphorothioate Oligonucleotidesras Proteins

Identifiers

PMID10468036
OpenAlexW82777483

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.