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ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women.

Steinwall, Margareta LU ; Åkerlund, Mats LU ; Bossmar, Thomas LU ; Nishii, M and Wright, M (2004) In BJOG: An International Journal of Obstetrics & Gynaecology2000-01-01+01:00 111(2). p.120-124
Abstract
Objective To determine the effect of ONO-8815Ly on uterine contractions.



Design A randomised, double-blind, placebo-controlled, dose-ascending, cross-over study.



Setting Department of Obstetrics and Gynaecology, University Hospital of Lund, Sweden.



Population Seventeen, healthy, parous and permanently sterilised women.



Methods Intrauterine pressure was recorded on days 1-3 of bleeding of two menstruations. Subjects were intravenously treated with 4 or 8 mug/minute of ONO-8815Ly or placebo for 130 minutes. Intravenous bolus injections of oxytocin, 50 pmol/kg body weight, were given 10 minutes before, during infusion after 60 and 120 minutes and 60 minutes after... (More)
Objective To determine the effect of ONO-8815Ly on uterine contractions.



Design A randomised, double-blind, placebo-controlled, dose-ascending, cross-over study.



Setting Department of Obstetrics and Gynaecology, University Hospital of Lund, Sweden.



Population Seventeen, healthy, parous and permanently sterilised women.



Methods Intrauterine pressure was recorded on days 1-3 of bleeding of two menstruations. Subjects were intravenously treated with 4 or 8 mug/minute of ONO-8815Ly or placebo for 130 minutes. Intravenous bolus injections of oxytocin, 50 pmol/kg body weight, were given 10 minutes before, during infusion after 60 and 120 minutes and 60 minutes after completion of infusion. The plasma concentrations of ONO-8815Ly were measured in samples obtained immediately before each oxytocin injection.



Main outcome measure Area under pressure recording curve (AUC) 10 minutes before and after each oxytocin injection.



Results Twelve women, six in each dose group, completed both recordings. Of these, two women of each group were not included in efficacy analysis due to non-responsiveness to oxytocin or missing baseline value. The AUC over 10 minutes before oxytocin injection after 60 minutes of infusion of ONO-8815Ly at 4 and 8 mug/minute was reduced to 21% and 37% of that before infusion, respectively. The AUC after oxytocin at that time amounted to 21% and 19%, respectively, of that before infusion. The activity and responsiveness remained low after 120 minutes but started to return to baseline 60 minutes after stopping infusion. Placebo had no effect.



Conclusions ONO-8815Ly is a potent inhibitor of spontaneous uterine contractility in non-pregnant women and it reduces the uterine response to oxytocin injections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BJOG: An International Journal of Obstetrics & Gynaecology2000-01-01+01:00
volume
111
issue
2
pages
120 - 124
publisher
Wiley-Blackwell
external identifiers
  • wos:000188798500005
  • pmid:14723748
  • scopus:0442291991
ISSN
1471-0528
DOI
10.1046/j.1471-0528.2003.00016.x
language
English
LU publication?
yes
id
f992982d-931f-42dd-9cb0-7de181d75275 (old id 120142)
alternative location
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=14723748&dopt=Abstract
date added to LUP
2007-07-18 11:31:46
date last changed
2017-05-28 04:16:19
@article{f992982d-931f-42dd-9cb0-7de181d75275,
  abstract     = {Objective To determine the effect of ONO-8815Ly on uterine contractions.<br/><br>
<br/><br>
Design A randomised, double-blind, placebo-controlled, dose-ascending, cross-over study.<br/><br>
<br/><br>
Setting Department of Obstetrics and Gynaecology, University Hospital of Lund, Sweden.<br/><br>
<br/><br>
Population Seventeen, healthy, parous and permanently sterilised women.<br/><br>
<br/><br>
Methods Intrauterine pressure was recorded on days 1-3 of bleeding of two menstruations. Subjects were intravenously treated with 4 or 8 mug/minute of ONO-8815Ly or placebo for 130 minutes. Intravenous bolus injections of oxytocin, 50 pmol/kg body weight, were given 10 minutes before, during infusion after 60 and 120 minutes and 60 minutes after completion of infusion. The plasma concentrations of ONO-8815Ly were measured in samples obtained immediately before each oxytocin injection.<br/><br>
<br/><br>
Main outcome measure Area under pressure recording curve (AUC) 10 minutes before and after each oxytocin injection.<br/><br>
<br/><br>
Results Twelve women, six in each dose group, completed both recordings. Of these, two women of each group were not included in efficacy analysis due to non-responsiveness to oxytocin or missing baseline value. The AUC over 10 minutes before oxytocin injection after 60 minutes of infusion of ONO-8815Ly at 4 and 8 mug/minute was reduced to 21% and 37% of that before infusion, respectively. The AUC after oxytocin at that time amounted to 21% and 19%, respectively, of that before infusion. The activity and responsiveness remained low after 120 minutes but started to return to baseline 60 minutes after stopping infusion. Placebo had no effect.<br/><br>
<br/><br>
Conclusions ONO-8815Ly is a potent inhibitor of spontaneous uterine contractility in non-pregnant women and it reduces the uterine response to oxytocin injections.},
  author       = {Steinwall, Margareta and Åkerlund, Mats and Bossmar, Thomas and Nishii, M and Wright, M},
  issn         = {1471-0528},
  language     = {eng},
  number       = {2},
  pages        = {120--124},
  publisher    = {Wiley-Blackwell},
  series       = {BJOG: An International Journal of Obstetrics & Gynaecology2000-01-01+01:00},
  title        = {ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women.},
  url          = {http://dx.doi.org/10.1046/j.1471-0528.2003.00016.x},
  volume       = {111},
  year         = {2004},
}