Linked Life Data

2107986

Source:http://linkedlifedata.com/resource/pubmed/id/2107986

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1990-5-2
pubmed:abstractText
We have previously explored induction of coronary thrombolysis with tissue-type plasminogen activator (t-PA) administered intramuscularly. Absorption-enhancing agents that rendered the approach feasible were identified, but large amounts of activator were required and initial elevations of concentrations in plasma could not be sustained. The present study was designed to determine whether more therapeutically favorable plasma concentrations could be induced by genetically engineering or chemically modifying t-PA to prolong its half-life based on the hypothesis that the ratio of absorption to clearance would be increased. Each of four genetically engineered variants (one variant with growth factor and kringle 1 domains deleted and kringle 2 duplicated, a second variant with a cysteine for Arg substitution in the growth factor domain, a third variant with an additional urokinase kringle inserted, and a fourth variant with the growth factor domain deleted) and enzymatically deglycosylated t-PA exhibited prolonged half-life after bolus intravenous injection in rabbits. Each elicited substantially higher and more sustained elevations in plasma after intramuscular injection in rabbits or dogs with absorption-enhancing agents as compared with wild-type t-PA that were not accompanied by a systemic lytic state. Thus, use of molecular variants of t-PA with prolonged half-lives in the circulation permits induction of augmented and sustained elevations of plasma concentrations after intramuscular injection with absorption-enhancing agents as compared with wild-type t-PA, rendering potentially therapeutic blood levels more attainable with relatively modest amounts of material.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0009-7322
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1362-73
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators.
pubmed:affiliation
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't