Fetal and maternal response to intravenous infusion of a thromboxane synthetase inhibitor.
Pharmacologic inhibition of thromboxane synthetase activity has reversed the clinical manifestations of toxemia in the ovine model. To investigate placental transfer and fetal effects of a selective thromboxane synthetase inhibitor, CGS13080 (Ciba-Geigy, Summit, N.J.) was intravenously infused into eight singleton- or twin-bearing ewes near term. During CGS 13080 infusion (0.1 mg/kg/hr), maternal steady-state CGS 13080 levels of 102 +/- 18 ng/ml were achieved within 30 minutes and maternal serum thromboxane generation decreased significantly (13 +/- 3 to 4 +/- 1 ng/ml). However, fetal serum levels of CGS 13080 were only 4% of peak maternal concentrations and fetal serum thromboxane generation did not change. There was no evidence of change in uterine blood flow, maternal or fetal blood pressure, heart rate, blood gas values, or fetal or maternal metabolites of prostacyclin or prostaglandin E2 during the study. We speculate that CGS 13080 may be efficacious in the treatment of human pregnancy-induced hypertension.
Cardin
J P
JP
Department of Obstetrics and Gynecology, Harbor-University of California at Los Angeles, Torrance 90509.
Ross
M G
MG
Ervin
M G
MG
Schaffer
A V
AV
Douglas
F L
FL
Simke
J P
JP
D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D011453:Prostaglandins / Q000097:blood*; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012756:Sheep; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D007166:Immunosuppressive Agents; D011453:Prostaglandins; D011725:Pyridines; C037787:pirmagrel; D013930:Thromboxane-A Synthase