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

Margareta Steinwall, Mats Åkerlund, Thomas Bossmar, Mikio Nishii, Makayla R. Wright
In: BJOG: An International Journal of Obstetrics & Gynaecology · 2004 · vol. 111(2) , pp. 120–124 · doi:10.1046/j.1471-0528.2003.00016.x · PMID:14723748 · W2145313836
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ONO-8815Ly, an EP2 agonist, markedly inhibited uterine contractions and reduced response to oxytocin in non-pregnant women.

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This randomized, double-blind, placebo-controlled, dose-ascending cross-over study examined the effects of the EP2 agonist ONO-8815Ly on uterine contractility in 17 healthy, parous, permanently sterilised non-pregnant women. Intrauterine pressure was recorded during menstruation days 1–3, and participants received intravenous ONO-8815Ly (4 or 8 μg/min) or placebo for 130 minutes, with oxytocin boluses given before and during the infusion; outcomes were quantified as the area under the pressure curve before and after each oxytocin dose. ONO-8815Ly markedly reduced spontaneous contractility and the uterine response to oxytocin, with AUC after infusion at 60 minutes falling to 21% and 37% of baseline before infusion for the lower and higher doses, respectively, and remaining low after 120 minutes but returning toward baseline 60 minutes after stopping. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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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 microg/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 microg/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.
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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) Links Related Resources Scopus publication: Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/120142 - author - Steinwall, Margareta LU ; Åkerlund, Mats LU ; Bossmar, Thomas LU ; Nishii, M and Wright, M - organization - publishing date - 2004 - type - Contribution to journal - publication status - published - subject - in - BJOG: An International Journal of Obstetrics & Gynaecology - 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 - 2016-04-01 15:30:08 - date last changed - 2025-10-14 10:10:47 @article{f992982d-931f-42dd-9cb0-7de181d75275, 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 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.}}, 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 & Gynaecology}}, title = {{ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women.}}, url = {{https://lup.lub.lu.se/search/files/4406823/623935.pdf}}, doi = {{10.1046/j.1471-0528.2003.00016.x}}, volume = {{111}}, year = {{2004}}, }

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