Placental transfer of the thromboxane synthetase inhibitor ridogrel in the late-pregnant ewe.
OBJECTIVE
To assess the occurrence of placental transfer of the thromboxane synthetase inhibitor ridogrel in the pregnant ewe and to determine its effect on prostanoid levels in the ewe and fetal lamb, on uterine contractility and on maternal and fetal hemodynamics.


METHODS
Five chronically instrumented pregnant ewes at 122 days of gestation received intravenous infusions of 5 mg/kg/3 h ridogrel and solvent. Maternal and fetal arterial samples were obtained at predetermined intervals to determine concentrations of ridogrel and prostaglandin metabolites TXB2, 6-keto-PGF1alpha, PGF2alpha, and PGE2. Maternal and fetal responses of blood flow and pressures were determined.


RESULTS
Fetal ridogrel levels were 25% of maternal concentrations. Ridogrel showed rapid and marked thromboxane synthetase inhibition and augmentation of levels of prostaglandin metabolites. There was no evidence of change in amniotic pressure, uterine blood flow, maternal and fetal blood pressure and heart rate.


CONCLUSIONS
Ridogrel is a potent thromboxane synthetase inhibitor which passes the sheep placenta, does not influence maternal and fetal hemodynamics and uterine contractility, and shows similar antiplatelet activity in the ewe and the fetal lamb.
Schneider
T J
TJ
Department of Obstetrics and Gynecology, School of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands.
Struijk
P C
PC
Wallenburg
H C
HC
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005865:Gestational Age; D010421:Pentanoic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011453:Prostaglandins / Q000097:blood*; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology; D012756:Sheep; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014590:Uterine Contraction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D010421:Pentanoic Acids; D011453:Prostaglandins; D011725:Pyridines; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C060219:ridogrel