Maternal and fetal cardiovascular effects and placental transfer of the oxytocin antagonist atosiban in late-gestation pregnant sheep.
OBJECTIVE
Atosiban is a synthetic oxytocin antagonist that is currently undergoing dose-ranging clinical trials. To date, no data are available on the cardiovascular effects of combined oxytocin and vasopressin 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 pharmacokinetics and the rate of placental transfer of atosiban.


METHODS
Five chronically catheterized pregnant sheep were treated with a 2-hour infusion of atosiban (300 micrograms.min-1) at 116 to 126 days' gestation. Maternal and fetal blood pressure and heart rate and uterine blood flow were measured before and during the infusion. Maternal and fetal arterial blood samples were obtained throughout the experiment for measurement of plasma atosiban levels and blood gas values.


RESULTS
No significant change in maternal cardiovascular parameters or uterine blood flow were observed. Similarly, no changes in fetal blood pressure and arterial blood gases were present during the infusion of the atosiban. 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 t1/2 alpha of 17 minutes and a mean t1/2 beta of 2.2 hours. Fetal plasma levels of atosiban were at or below the detection limit.


CONCLUSIONS
Atosiban does not significantly affect maternal or fetal cardiovascular parameters when it is administered for 2 hours in late-pregnant sheep. Although significant levels were measured in maternal blood, negligible transfer to the fetus occurred.
Greig
P C
PC
Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, Winston-Salem, North Carolina.
Massmann
G A
GA
Demarest
K T
KT
Weglein
R C
RC
Holland
M L
ML
Figueroa
J P
JP
D000818:Animals; D001158:Arteries; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002319:Cardiovascular System / Q000187:drug effects* / Q000196:embryology; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000098:blood supply / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008431:Maternal-Fetal Exchange; D010100:Oxygen / Q000097:blood; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000098:blood supply / Q000187:drug effects; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
C047046:atosiban; D002245:Carbon Dioxide; D010121:Oxytocin; D010100:Oxygen; D014668:Vasotocin