MATERNAL AND FETAL CARDIOVASCULAR EFFECTS AND PLACENTAL-TRANSFER OF THE OXYTOCIN ANTAGONIST ATOSIBAN IN LATE-GESTATION PREGNANT SHEEP

OBJECTIVES: Atosiban is a synthetic oxytocin antagonist that is curren tly undergoing dose-ranging clinical trials. To date, no data are avai lable on the cardiovascular effects of combined oxytocin and vasopress in blockade during late pregnancy. Our aims were (1) to determine the effects of atosiban infusion on the maternal and fetal cardiovascular system and on uterine blood flow and (2) to determine the maternal pha rmacokinetics and the rate of placental transfer of atosiban. STUDY DE SIGN: Five chronically catheterized pregnant sheep were treated with a 2-hour infusion of atosiban (300 mug . min-1) at 116 to 126 days' ges tation. Maternal and fetal blood pressure and heart rate and uterine b lood flow were measured before and during the infusion. Maternal and f etal arterial blood samples were obtained throughout the experiment fo r measurement of plasma atosiban levels and blood gas values. RESULTS: No significant change in maternal cardiovascular parameters or uterin e blood flow were observed. Similarly, no changes in fetal blood press ure and arterial blood gases were present during the infusion of the a tosiban. Maternal plasma levels of atosiban reached a maximum of 585.2 +/- 82.2 (ng/ml mean +/- SD) at the end of the infusion and decreased biexponentially with a mean t1/2alpha of 17 minutes and a mean t1/2be ta of 2.2 hours. Fetal plasma levels of atosiban were at or below the detection limit. CONCLUSION: Atosiban does not significantly affect ma ternal or fetal cardiovascular parameters when it is administered for 2 hours in late-pregnant sheep. Although significant levels were measu red in maternal blood, negligible transfer to the fetus occurred.