Transplacental passage of a progesterone antagonist in monkeys.
The progesterone antagonist RU 486 dramatically increases myometrial contractility of the pregnant uterus, making it a potential adjunctive therapy for labor induction or therapeutic pregnancy termination. Sixteen female cynomolgus monkeys were studied during the second or third trimester of pregnancy. Hysterotomies were performed with the animals under anesthesia, providing access to the intact placental vasculature. RU 486 (25 mg) was injected intravenously into the mothers. Serial blood samples were drawn from the maternal and fetal-placental compartments for a period of 2 hours. RU 486 achieved a gradient equilibrium between the maternal and fetal-placental circulation within 5 minutes, suggesting free passage by simple diffusion. The clearance kinetics of immunoreactive RU 486 are consistent with an open three-compartment system in mother and fetus. The fetal-placental index decreased from 31.2% to 17.8% between the second and the third trimester of pregnancy. There was no acute toxicity of the RU 486 noticed during the experimental course.
Wolf
J P
JP
Department of Obstetrics and Gynecology, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk 23507.
Chillik
C F
CF
Itskovitz
J
J
Weyman
D
D
Anderson
T L
TL
Ulmann
A
A
Baulieu
E E
EE
Hodgen
G D
GD
D000818:Animals; D004963:Estrenes / Q000493:pharmacokinetics*; D005260:Female; D008252:Macaca fascicularis; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D015735:Mifepristone; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011372:Progestins / Q000037:antagonists & inhibitors*
D004963:Estrenes; D011372:Progestins; D015735:Mifepristone