Effects of ridogrel on the prostacyclin-thromboxane ratio in nulliparous third trimester-pregnant rhesus monkeys.
The effects of ridogrel, a thromboxane synthetase inhibitor and endoperoxide receptor antagonist, were studied in twelve pregnant, nulliparous Rhesus monkeys (Macaca mulatta) during the last trimester of pregnancy. Ridogrel was administered intravenously in two groups of animals (n = 6), at either 0.1 mg/kg or 1.0 mg/kg. Ultrasonic assessment of the fetuses during and after the infusion period revealed no obvious changes in fetal condition. Both dosages reduced serum thromboxane levels 30 minutes after administration, 96.6% and 99.6% suppression, 0.1 mg/kg and 1.0 mg/kg, respectively (P < 0.0001), while the 1.0 mg/kg dose produced continued suppression for 24 hours (78% suppression, P < 0.0001) and was lower than the 0.1 mg/kg 24 hour value (P < 0.008). Prostacyclin levels increased to 340% and 472% of baseline values, 0.1 mg/kg and 1.0 mg/kg, respectively at 30 minutes and to 928% and 255% of baseline at 24 and 48 hours after treatment in the 1.0 mg/kg group (P < 0.0003). Ridogrel caused no changes in maternal or neonatal outcome. The potential for the use of this compound for the treatment of preeclampsia is discussed.
Keith
J C
JC
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute, Blacksburg 24061.
Goodrich
J A
JA
Endo
Y
Y
Taub
D
D
Mehlman
P
P
Ward
G
G
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D008253:Macaca mulatta; D010421:Pentanoic Acids / Q000494:pharmacology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal / Q000097:blood*; D011725:Pyridines / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D010421:Pentanoic Acids; D011725:Pyridines; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C060219:ridogrel