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

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.